bluuebunny/crossref_metadata_2025 huggingface dataset:
Bronchial Sensitization in Ginea Pigs following Ingestion of Ovalbumin
Authors: Riedel F. , Kanter N. , Schauer U. , Petzoldt S. , Rieger C.H.L.
Published: August 2009

Local bronchial mucosal hypersensitivity following antigen feeding was studied in the guinea pig. Groups of 6 animals were fed 1% ovalbumin (OA) in tap water or tap water without antigen (control group) for different feeding periods (14, 28, 42, and 56 days). Inhalative provocations with increasing concentrations of OA (0.5–8% OA) were performed at the end of each feeding period followed by body plethysmographic measurement of airway obstruction. Specific bronchial hypersensitivity to inhaled OA was not found in the control group, whereas specific bronchial reactivity to OA, described as reactivity index, was significantly different from the control group after 14 (p <0.05), 28 (p <0.001) and 42 days (p <0.01) of feeding. No difference to the control group was found after 56 days of feeding. Anti-OA IgG total and IgG1 in serum and bronchoalveolar lavage fluid were increased in OA-fed animals reaching maximal concentrations at day 28 of the feeding period. We conclude that oral feeding of a 1 % solution of OA can induce a transient state of local hypersensitivity to inhaled antigen in the guinea pig as manifested by bronchoconstriction on OA inhalation and increased concentrations of local and systemic specific antibodies. This period of local hypersensitivity is followed by tolerance.
High-Incidence of C9 Deficiency throughout Japan: There Are No Significant Differences in Incidence among Eight Areas of Japan
Authors: Hayama Kenji , Sugai Nagae , Tanaka Shoji , Lee Shiei , Kikuchi Hiroaki , Ito Jin , Suzuki Junzo , Nagata Yasushi , Kondo Hozumi , Harayama Osamu , Tuzuki Kazuo , Yoshida Shoji , Fujita Mitsue , Ohmori Fumihiko , Kawai Tadashi , Akagaki Yohji , Inai Shinya
Published: August 2009

From 92,686 sera sent from hospitals throughout Japan to the Special Reference Laboratories, for CH50 assay, we were able to classify 80 patients as C9-deficient using a sensitive screening test, as well as hemolytic and immunochemical C9 assays. The incidence of C9 deficiency was determined to be 0.086%, and there were no distinct differences among the eight areas of Japan tested. Serum CH50 levels of these C9-deficient patients varied widely (9.4–63.8 U/ml), and exhibited a higher value (average: 34.1 U/ml) than that of healthy C9-deficient individuals, probably due to elevated C3, C4, and C5 levels. These patients suffered from a variety of autoimmune, renal, and infectious diseases, which, however, are thought to be only incidentally associated with C9 deficiency.
Comparative Immunochemical Analysis of Five Thermoactinomyces Strains
Authors: Ylönen J.K. , Ojanen T.H. , Jägerroos H.J.W. , Mäntyjärvi R.A.
Published: August 2009

The antigen structures in mycelial extracts of 4 strains of Thermoactinomyces vulgaris and 1 strain of Thermoactinomyces candidus were compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining. For immunological characterization, antigens were transferred electrophoretically to nitrocellulose membranes and blotted with T. vulgaris strain-specific antisera and with sera of farmer’s lung patients. Cross-reactions between the strains were also studied using immunodiffusion and crossed immunoelectrophoresis. Protein components between 50 and 60 kilodaltons were found to be the most immunogenic. Patient sera showed heterogeneous responses, but all reacted with an antigen at 55 kilodaltons that was also common to all strains studied.
Relationship between Anti-IgE Autoantibody and Severity of Bronchial Asthma
Authors: Iwamoto Itsuo , Nawata Yasushi , Koike Takao , Tanaka Makoto , Tomioka Hisao , Yoshida Sho
Published: August 2009

To determine whether anti-IgE autoantibody (algE) is involved in modulating allergic asthma, we examined the relationship between the titers of algE and severity of asthma in 63 allergic asthmatics. The titer of algE in patients’ sera was 14.4 ± 17.9 units (mean ± SD). Thirty-one patients had algE greater than 5 units (26.4 ± 22.1 units), whereas 32 patients had algE less than 5 units (2.0 ± 0.9 units). Patients with high algE (greater than 5 units) were less severe than those with low algE (less than 5 units) (1.65 ± 0.42 and 2.19 ± 0.52 of severity score, respectively; p <0.01). There was an inverse correlation between the titers of algE and the severity scores (r = ––0.328; p <0.01). Patients with high algE also had lower bronchial reactivity to methacholine than those with low algE (556 ± 292 and 170 ± 182 μg/ml of threshold dose of inhaled methacholine, respectively; p <0.005). There was a significant correlation between the titers of algE and the threshold dose of methacholine (r = 0.499; p <0.01). These findings suggest that algE plays a protective role in bronchial hyperreactivity in allergic asthma.
Epidemiology of the Allergic Diseases: Are They Really on the Increase?
Authors: Wüthrich Brunello
Published: August 2009

Epidemiological studies on representative populations clearly demonstrate a significant general increase of atopic diseases during the last decades, mainly for pollinosis. For the manifestation of an atopic disease both allergen exposure, which leads to specific IgE antibody formation, and the presence of additional realization factors are required. The nature of the latter is still partially unknown. Careful interpretations of clinical and experimental observations show that besides indoor and outdoor pollution, increased exposure to allergens through changes in human way of living is an important cofactor responsible for the increased incidence of atopic diseases.
Asthma Pharmacology: Industrial/Clinical Interface
Authors: Morley J.
Published: August 2009

The disease of asthma remains poorly understood. Hence, considerable latitude has been afforded to pharmacologists concerned to identify novel compounds for development as anti-asthma drugs. Compounds can be selected (1) on the basis of known efficacy as bronchodilator (beta-adrenoceptor agonists, parasympatholytics and xanthines) and prophylactic (cromoglycate and ketotifen) or anti-inflammatory (glucocorticosteroids) actions; (2) by reference to current theories of asthma pathogenesis, e.g., inhibition of the formation and action of autoacoids (leukotrienes, platelet-activating factor) or cytokines (GM-CSF, IL-5), or (3) by reference to hitherto unexplored physiological processes (K+ channel activation, PDE isoenzyme inhibition, selective immunosuppressive actions). There is a need to test whether the rationale for drug selection is justified. This can only be resolved by study of asthma patients, since normal subjects may respond inappropriately. Thus, normal subjects do not exhibit airway obstruction or airway hyperreactivity and hence do not respond to bronchodilator substances. Similarly, normal subjects respond to platelet-activating factor with a cellular infiltrate in which neutrophils predominate in contrast to atopic asthmatics who exhibit an eosinophilia. It follows that compound discovery and evaluation must be an iterative procedure in which animal studies are supplemented by clinical studies and vice versa. This is most readily achieved by establishing clinical research that is a complementary to preclinical research.
New Perspectives in the Modulation of Allergic Inflammation
Authors: de Weck A.L. , Stadler B.M. , Dahinden C.A.
Published: August 2009

Studies on the regulation of IgE synthesis by IgE cellular receptors or fragments thereof, the so-called IgE-binding factors, are currently attracting much attention. Even more important may be some lymphokines such as interleukin 4 and interferon gamma which have been shown to have opposite influences on IgE synthesis, both in vitro and in vivo. However, the role of anti-isotypic anti-IgE antibodies, which have been shown to occur frequently during an IgE response, also deserves to be further investigated. At the effector level, namely the development of immediate and late allergic reactions following renewed encounter with allergen, new concepts such as variable releasability and priming of effector cells by lymphokines have opened new investigative pathways. Indeed, pretreatment of neutrophils by granulocyte/monocyte colony-stimulating factor or basophils by interleukin 3 appears essential for production or optimal release of inflammatory mediators such as histamine, leukotrienes, or platelet-activating factor. Even the successive impact of purified lymphokines such as interleukins 3 and 8 on basophils may suffice to initiate mediator release. These phenomena may explain, at the molecular level, the induction of a state of hyperreactivity characteristic of the late-phase allergic reaction. They also suggest new immunopharmacological approaches for the treatment of allergy.
Biological Role of Different Antibody Classes
Authors: Spiegelberg Hans L.
Published: August 2009

Antibodies are divided into different classes and subclasses (isotypes) according to structural differences in the constant region of the heavy polypeptide chains. The different isotypes mediate specific biologic functions that are important for the response to pathogens and in the pathogenesis of immunological diseases such as allergies. The numbers of different isotypes vary in different species, humans have 9 different Ig classes and subclasses. Of these 9, only IgM, IgG1, IgG2 and IgG3 activate the classical pathway of complement. All four IgG and both IgA subclasses, but not IgM, IgE and IgD, bind to Fc receptors on neutrophils, and induce the release of granule enzymes. All four IgG subclasses but no other Ig isotype induce serotonin release from platelets. In man, only IgE binds to the high-affinity Fc receptors (FcεRI) on mast cells and basophils and induces histamine and leukotriene release. IgE also binds to low-affinity Fc receptors (FcεRII) on lymphocytes, monocytes and eosinophils; however, the functions of FcεRII on these cells are not fully established. Monocytes from patients with atopic dermatitis that express more FcεRII than monocytes from normals do not release more LTC4 than monocytes from nonallergic healthy humans after activation with aggregated IgE. IgG and IgA are more efficient than IgE in inducing the release of mediators of inflammation from monocytes. The antibody response to certain antigens such as carbohydrates and allergens are often restricted to IgG2 and IgG1, IgG4 and IgE, respectively. Although the control of the Ig class expression is not understood, it was recently shown that interleukin-4 (IL-4) secreted by T helper cells plays a major role in the human IgM to IgG4 and IgE switch mechanism, both isotypes being characteristics for antibodies to allergens. However, the reason why allergens activate predominantly T helper cells secreting IL-4 is unknown. It may be because allergens are processed by special antigen-presenting cells that cause T helper cells to differentiate into IL-4-secreting cells.
IgE and Inflammatory Cells: The Cellular Networks in Allergy
Authors: Dessaint Jean-Paul , Capron André
Published: August 2009

The expression by macrophages, eosinophils, and platelets of IgE receptors (FcεRII) confers on these cells, present or recruited at the site of allergen challenge, a direct role in the development of adverse allergic reactions. The IgE-dependent activation of macrophages, eosinophils, and platelets is moreover inhibited by antiallergic drugs such as disodium cromoglycate or nedocromil. This network of IgE-dependent effector cells is controlled by immunoregulatory pathways which can be target of desensitization therapy. Contrary to their deleterious role in allergic disorders, IgE- and FcεRII-bearing cells play a decisive role in the immune defense against helminth parasites, therefore pointing to a dualistic function of IgE.
Role of Langerhans Cells in Atopic Disease
Authors: Bruijnzeel-Koomen C.A.F.M. , Fokkens W.J. , Mudde G.C. , Bruijnzeel P.L.B.
Published: August 2009

So far, the role of antigen-presenting cells in atopic disorders has been underestimated. Recent observations, made in the skin of patients with atopic dermatitis and in the nasal mucosa of patients with allergic rhinitis suggest that Langerhans cells, being tissue-specific dendritic cells with potent antigen-presenting capacity, play an important role in the allergic inflammatory response. Evidence is presented that Langerhans cells even play a crucial role in directing the type of the allergic reaction mechanism.
Contribution of Eosinophil-Derived Mediators in Asthma
Authors: Bruijnzeel P.L.B.
Published: August 2009

The most important eosinophil-derived mediators which may contribute to the pathogenesis of asthma are: major basic protein, eosinophil cationic protein, eosinophil peroxidase, reactive oxygen species, leukotriene C4, and platelet-activating factor. The potency of the eosinophil to release these mediators can be greatly enhanced by eosinophil mobilizing and activating factors such as granulocyte macrophage colony stimulating factor, interleukins 3 and 5, platelet-activating factor, and perhaps leukotriene B4. For the development of more effective anti-asthma drugs it, therefore, seems relevant to unravel and interfere with the steps of eosinophil activation.
Effects of Monocyte- and Macrophage-Derived Products on Granulocyte Function in Asthma
Authors: Wilkinson James R.W. , Howell Caroline S. , Lee Tak H.
Published: August 2009

The pathology of bronchial asthma demonstrates a multicellular process. The airway mucosa is infiltrated with both mononuclear cells and granulocytes, of which the eosinophil is particularly prominent. In order to elucidate the cellular biology of airways inflammation, it is important to understand the interactions between different cells, as well as the biology of each individual cell type. The review highlights the effects of monocyte-macrophage-derived cell products on granulocyte function, because of the evidence for monocyte/macrophage activation in bronchial asthma.
Aspirin-Induced Asthma: New Insights into Pathogenesis and Clinical Presentation of Drug Intolerance
Authors: Szczeklik Andrew
Published: August 2009

Aspirin-induced asthma (AIA) is a distinct clinical syndrome, present in about 10% of adult asthmatics. Precipitation of the asthmatic attacks by aspirin and other nonsteroidal anti-inflammatory drugs is the hallmark of the syndrome. The idea that the attacks might result from the specific inhibition of a single enzyme in the respiratory tract, namely cyclooxygenase, has found support in experimental and clinical studies, and has generated a number of new hypotheses on the mechanism of bronchoconstriction. These hypotheses, operating within the frame of cyclooxygenase theory, point to the involvement of leukotrienes, platelets or chronic viral infection. Progress in studies on AIA has improved our knowledge on the drugs – safe and contraindicated – in this relatively common and fascinating clinical syndrome. Studies on mechanisms operating in AIA might eventually lead to new insights in pathogenesis of bronchial asthma.
Mapping of Epitopes on Poa p I and Lol p I Allergens with Monoclonal Antibodies
Authors: Lin Zhengwei , Ekramoddoullah Abul K.M. , Jaggi Kuldeep S. , Dzuba-Fischer Jacqie , Rector Edward , Kisil Fred T.
Published: August 2009

Allergen Poa p I isolated from the dialysed aqueous extract of Kentucky blue grass pollen by affinity chromatography with an anti-Lol p I murine monoclonal antibody (MAb) 290A-167 was previously shown to consist of a 35.8-kilodalton (kD) component with a pI of 6.4, designated as Poa p Ia, and a 33-kD component with a pI of 9.1, designated as Poa p Ib. The present study reports on the comparative antigenic analyses of these two components, using MAbs produced separately against Poa p I and Lol p I. Thus, anti-Poa p I MAbs 60 and 61 and anti-Lol p I MAb 290A-167 recognized Poa p Ia and Poa p Ib whereas anti-Poa p I MAbs 62, 63 and 64 and anti-Lol p I MAb 348A-6 recognized only Poa p Ia. The specificities of the MAbs were further resolved by comparing their respective abilities to inhibit the binding of 125I-Poa p I or 125I-Lol p I to the different MAbs prepared in the form of solid phase. These studies revealed that at least 4 distinct epitopes (designated as E1, E2, E3 and E4) were shared by both Poa p I and Lol p I. All 4 epitopes were present on Poa p Ia whereas only E1 and E3 were detected on Poa p Ib. E1 was recognized by MAbs 60 and 61, E2 by MAbs 62, 63 and 64, E3 by MAb 290A-167 and E4 by MAb 348A-6. The observations that MAb 290A-167 inhibited significantly the binding of human IgE antibodies to Poa p I and Lol p I were interpreted to indicate that epitope E3 may also constitute an allergenic site on both Poa p I and Lol p I. These studies revealed that Poa p I and Lol p I share extensive antigenic and allergenic cross-reactivities with one another.
Hyposensitization Therapy with Whole Pollen Extract or Purified Allergens Monitored by Immunoblotting
Authors: Jarolim Erika , Matthiesen Finn , Stahl Skov Per , Tejkl Margarete , Oesterballe Ole , Poulsen Lars K.
Published: August 2009

Patients allergic to grass pollen were hyposensitized with two major allergenic components or whole extract of timothy grass pollen. Specific IgE, IgG1, and IgG4 formed during immunotherapy were analyzed by immunoblotting. Similar antibody-binding patterns were observed in both patient groups. Inhibition experiments using allergenic components isolated by preparative sodium dodecyl sulphate-polyacrylamide gel electrophoresis indicated that all antigenic components of timothy grass pollen detected in immunoblot dispose of private and cross-reactive determinants for binding of human IgE. The worse clinical outcome of immunotherapy after hyposensitization with two cross-reactive components did, therefore, not correlate with a specific antibody formation pattern.
Platelet-Activating Factor-Induced Activation and Cytoskeletal Change in Cultured Eosinophils
Authors: Ebisawa Motohiro , Saito Hirohisa , Iikura Yoji
Published: August 2009

The culture of mononuclear umbilical cord blood cells with low concentrations of interleukin-3 (IL-3) and interleukin-5 (IL-5) for 3 weeks or more results in the consistent production of large numbers of eosinophils. Density distribution analysis and electron microscopic analysis revealed the characteristics of cultured eosinophils to be partially different from peripheral eosinophils. In modified Boyden chamber studies, cultured eosinophils exhibited locomotive activity in response to platelet-activating factor (PAF), with a peak response at 10––6M, but not to N-formyl-L-methionyl-L-leucyl-L-phenylalanine. PAF-induced changes in intracellular calcium concentrations in peripheral eosinophils and cultured eosinophils were similar. PAF-induced actin polymerization was observed in cultured eosinophils for the first 30 s followed by depolymerization for the next 10 min. These results suggest that cultured eosinophils respond to PAF in a manner analogous to peripheral eosinophils, and will be useful for in vitro studies.
Site of Nonrestrictive Binding of SEA to Class II MHC Antigens
Authors: Pontzer Carol H. , Russell Jeffry K. , Jarpe Michael A. , Johnson Howard M.
Published: August 2009

We have used the synthetic peptide approach to show that the N-terminal 45-amino acids of staphylococcal enterotoxin A (SEA), SEA(1–45), constitute an important part of its binding site on class II major histocompatibility complex (MHC) molecules. SEA(1–45) and to a lesser extent SEA(1–27) were able to displace SEA from HLA-DR on Raji cells as assessed by flow cytometry and to compete with radiolabeled SEA for interaction with HLA-DR in a direct binding assay. Specific binding of SEA to la on murine A-20 cells could be inhibited by the same peptides [i.e. SEA(1–45) > SEA(1–27)] that blocked binding to HLA-DR. Therefore, different class II MHC molecules associate with the same functional site on SEA. Further, an ELISA system was used to demonstrate that SEA(1–45) is able to directly bind to a mouse synthetic I-Aβb peptide, I-Aβb (65–85), which contains a binding site of the class II MHC molecule involved in SEA presentation to T cells. Thus, we have localized a site on SEA that is involved in selective surface association with class II MHC antigens and identified the region on the class II MHC antigen to which that site binds.
Progesterone Triggers Selective Mast Cell Secretion of 5-Hydroxytryptamine
Authors: Vliagoftis Harissis , Dimitriadou Violetta , Theoharides Theoharis C.
Published: August 2009

Mast cells are involved in allergic reactions where they secrete numerous mediators in response to immunoglobulin E and antigen. However, they have recently been implicated in neuroinflammatory conditions with a higher prevalence in women, and there have been clinical reports of progesterone anaphylaxis. When tested on purified rat peritoneal mast cells, progesterone alone stimulated release only of 5-hydroxy-tryptamine (serotonin) in a dose- and time-dependent manner. Serotonin release by progesterone was exceptional because it was not accompanied by histamine release or degranulation and was either augmented or unaffected by drugs which inhibit secretion induced by the classic mast cell secretagogue, compound 48/80. These findings indicate that mast cells are capable of selective serotonin secretion, previously shown only after pretreatement with certain tricyclic drugs, and may be involved in neuroendocrine syndromes.
Mast Cell Activation by Hornet (Vespa orientalis) Venom
Authors: Barenholz-Paniry Vered , Ishay Jacob S. , Pick Israel A. , Hammel Ilan
Published: August 2009

As far as its effect on the activation of rat peritoneal mast cells is concerned, the venom of young hornets (age 0–24 h) differs from that of adult hornets (over 24 h of age). ‘Juvenile’ venom caused activation mainly in rats previously sensitized to it, whereas ‘adult’ venom induced activation regardless of presensitization. Furthermore high concentrations of ‘adult’ venom were cytotoxic to the entire murine peritoneal cell population, but ‘juvenile’ venom was not toxic. SDS-PAGE data demonstrate that the venom of young hornets contains a unique component (82 kD), nonexistent in adult venom. Our data demonstrate that hornet venom activity is correlated with the hornet’s age.
The Pathology of the Autologous Serum Skin Test Response in Chronic Urticaria Resembles IgE-Mediated Late-Phase Reactions
Authors: Grattan C.E.H. , Boon A.P. , Eady R.A.J. , Winkelmann R.K.
Published: August 2009

The wheal-and-flare response to intradermal autologous serum in chronic urticaria offers a model for study of the pathogenesis of the disorder. Serial biopsies of autologous serum induced wheals were performed in 5 chronic urticaria patients to assess the evolution of the cellular inflammatory response and to look for evidence of mast cell degranulation. Perivascular neutrophils and eosinophils were seen as early as 30 min, becoming more intense and diffuse over 2 h. T lymphocyte numbers were increased by 2 h, CD4+ cells outnumbering CD8+ cells at 24 h. By 48 h, the neutrophils were clearing, but eosinophils and lymphocytes persisted. The histology of compound 48/80-induced wheals was similar to serum-induced wheals, but there was little or no response to physiological saline (0.16 M). Stainable mast cells were reduced in compound 48/80- and serum-induced wheals when compared to saline skin tests. Mast cell granules appeared swollen and had lost their characteristic lamellar substructure on electron microscopy of a serum-induced wheal biopsied at 10 min. Eosinophil degranulation was also observed at 2 h. The resemblance of the inflammation to the late phase of IgE-mediated immediate hypersensitivity reactions in atopies supports the concept that a circulating factor causes mast cell degranulation in chronic urticaria and may be important in the pathogenesis of the disorder.
Lack of Correlation between Mast Cell Response and Active Anaphylaxis in Mice
Authors: Justus David E. , Lemmons Kevin W. , Anderson Gary L.
Published: August 2009

Mast cell-competent mice, sensitized to lysozyme, were examined for their mast cell and anaphylactic responses to determine whether anaphylactic shock could occur independent of mast cell participation. Tissues (cremaster muscle, subdermal connective tissue and mesentery), taken a short time after intravenous antigenic challenge, showed no evidence of mast cell degranulation above control tissues. Data obtained from a quantitative comparison of the onset and increase in local and systemic anaphylactic and mast cell sensitivities to the antigen provide strong support for the view that mast cells are not the major effector cells for systemic anaphylaxis in mice. The significant increase in blood pressure that occurred immediately after infusion with the antigen also indicates that other cells within the blood stream are involved.
Immune Response to Endotoxin Isolated from Bacteroides fragilis in the Pregnant Guinea Pig
Authors: Beckmann Ilse , Meisel-Mikolajczyk Felicja , Leszczynski Piotr , Wallenburg Henk C.S.
Published: August 2009

The humoral immune response to endotoxin isolated from Bacteroides fragilis was analyzed in the pregnant guinea pig by means of passive hemagglutination, passive hemolysis, a modified Coombs test, and by crossed immunoelectrophoresis. Pregnant animals were immunized with endotoxin on day 30 of gestation, and antibodies were determined on day 61 in maternal and fetal sera, and in amniotic fluid. The IgG and IgM responses in maternal sera were of the same magnitude as in sera of nonpregnant animals. Fetal sera contained IgG and sometimes IgM, and a higher percentage of incomplete antibodies against endotoxin than maternal sera. Low-titer anti-endotoxin antibodies, partially sensitive to dithiothreitol, were found in amniotic fluid. A statistically significant reduction in the growth of fetuses from endotoxin-immunized females was observed.
Generation and Metabolism of Leukotrienes in Granulocytes of Patients with Cystic Fibrosis
Authors: Saak Armin , Schönfeld Wolfgang , Knöller Jürgen , Steinkamp Graciana , von der Hardt Horst , König Wolfgang
Published: August 2009

We studied the generation and metabolism of lipoxygenase products in peripheral granulocytes from children suffering from cystic fibrosis (CF). Peripheral granulocytes were stimulated at different times (days) before and during anti-infectious treatment with the Ca ionophore (7.5 μM, 5 and 20 min), opsonized zymosan (2 mg) and arachidonic acid (50 μM); the amount of lipoxygenase products in the cell supernatants was determined by high performance liquid chromatography. Granulocytes from patients with CF, compared to an age-matched control group, showed an increased ω-oxidation of the synthesized leukotriene (LTB4) into 20-OH- and 20-COOH-LTB4 after stimulation with the Ca ionophore (ratio of LTB4 versus ω-oxidated products in patients with CF: 0.77 ± 0.07, mean ± SEM, n = 11; control group: 1.07 ± 0.1, n = 11, p < 0.01) whereas the combined amounts of LTB4 and its ω-oxidated products did not differ significantly. A comparable profile was observed with opsonized zymosan. Stimulation of the cells with the Ca ionophore combined with arachidonic acid led to a significantly increased formation of lipoxygenase products in the patient group, whereas only a slight enhancement was observed in the control group. During the 14-day anti-infectious treatment a normalization of the altered pattern was observed. 12-Hydroxyeicosatetraenoic acid (12-HETE) production from platelets within the granulocyte fraction was significantly depressed in the CF group compared to the controls (38.5 ± 12.5 versus 339 ± 93 ng/5 ± 106 cells, p < 0.005). Within the CF group a strong correlation between the release of LTB4 and its metabolites, the production of 12-HETE and clinical (e.g. pO2, FEV1) and laboratory findings (e.g. IgE and IgG levels, C-reactive protein) was established. Our data suggest that the inflammatory process in patients with CF is associated with an alteration of the lipoxygenase pathway of granulocytes which correlates with the clinical signs of inflammation.
Inhibition of Histamine Release from Rat Peritoneal Mast Cells by MY-1250, an Active Metabolite of Repirinast (MY-5116)
Authors: Takei M. , Endo K. , Takahashi K.
Published: August 2009

MY-1250, an active metabolite of Repirinast (MY-5116), strongly and dose-dependently inhibited the in vitro histamine release from rat peritoneal mast cells induced by antigen. The IC50 value of MY-1250 for histamine release was in the order of 0.3 μM. Moreover MY-1250 strongly inhibited calcium ion mobilization from the intracellular Ca2+ store. In the presence of 3.6 × 10––5M of MY-1250, the initial rise in [Ca2+]i reached a maximum of only 13 nM, and the inhibitory effect was 81% for the initial rise. The IC50 value for this event was 0.25 μM. The inhibitory effect of MY-1250 on the initial rise in [Ca2+]i was closely correlated with that on histamine release.
MTT Colorimetric Assay Detects Mitogen Responses of Spleen but not Blood Lymphocytes
Authors: Chen Chung-Hua , Campbell Priscilla A. , Newman Lee S.
Published: August 2009

In an effort to simplify methods for assessing mitogen stimulation of blood lymphocytes, the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) colorimetric assay [1] was compared with the conventional tritiated thymidine deoxyriboside (3H-TdR) incorporation assay. Although able to detect mitogen responses by mouse and rat spleen cells, the MTT assay did not reliably measure blood mononuclear cell responses in mouse, rat or man. The 3H-TdR incorporation assay was effective in every case. Modifications of the MTT assay procedure did not rectify this disparity, which was caused in part by high MTT optical density readings by unstimulated cells. The inability of the MTT assay to detect mitogen responses by blood cells seems to reflect a species-independent physiologic property of these cells.
Common German Cockroach Whole Body and Fecal Allergens: Immunoprint Inhibition Studies
Authors: Homer Elliott , Kailas Jyothi , Stankus Richard P. , Lehrer Samuel B.
Published: August 2009

Previous studies have established that cockroach allergens are important sensitizing agents in the induction/exacerbation of urban asthma. The present investigation compared saline extracts of German cockroach (Blattella germanica) whole bodies (GWBE) and feces (GFE) as important sources of allergens. Both extracts were tested prior to or following gel filtration on Sephadex G-75 (Fr2). Immunoprinting of unfractionated fecal extract using 10 RAST-positive sera detected a series of allergens with pI values between 4.15–4.55 and a single allergen that focused near the cathode. Multiple allergens were detected in both GWBE-Fr2 and GFE-Fr2. Generally, most RAST-positive sera reacted similarly, although GWBE-Fr2 had more allergenic proteins than GFE-Fr2 with pI < 4.7 and fewer allergens with pI > 4.7. Immunoprint inhibition of GWBE and GFE by GWBE and GFE also demonstrated allergenic similarity, although homologous extracts were more effective inhibitors than heterologous preparations. Collectively, these studies demonstrate the allergenic similarities of cockroach whole body and fecal extracts. Thus fecal material may provide an important source of sensitizing antigen.
Alpha-Interferon Induces Cortisol Release by Human Adrenals in vitro
Authors: Cardoso Estela , Arzt Eduardo , Coumroglon Maria , Andrada Enia Comini , Andrada Juan A.
Published: August 2009

It is at present not clear whether alpha interferon (INF-α) can participate in the control of glucocorticoid blood levels through direct action on the adrenal gland. In this study, the possible action of INF-α on cortisol release by adrenal tissue was tested in vitro. Slices of normal human adrenals were incubated with INF-α for 3 h at 37°C in 95% air and 5% CO2. Cortisol release by adrenal tissue was stimulated by INF-α, showing a dose-response curve from 20 IU/ml, the lowest dose that gave a response, to a maximal dose of 60 IU/ml when the response reached a plateau. The effect of INF-α on cortisol liberation by adrenal tissue in vitro may be implied in neuroimmune regulatory interactions.
CI-959, a New, Potential Antiallergic Drug, Inhibits Mediator Release from Lung and Contractions of Human Airways in vitro
Authors: Adolphson R.L. , Schellenberg R.R. , Thueson D.O. , Conroy M.C.
Published: August 2009

Many symptoms of the immediate allergic response can be attributed to the synthesis/release and subsequent actions of histamine and metabolic products of arachidonic acid oxidation. CI-959 [5-methoxy-3-(1-methylethoxy)-N-1H-tetrazole-5-yl-benzo(b)thiophene-2-carboxamide], a new, potential antiallergic drug, inhibited the release of histamine, immunoreactive sulfidopeptide leukotrienes C4, D4 and E4 and im-munoreactive thromboxane B2 from immunologically activated guinea-pig and human lung cells in vitro. The IC50s of CI-959 using guinea-pig lung were: histamine, 0.8 ± 1.4 μM; leukotriene, 0.7 ± 1.6 μM and thromboxane, 9.6 ± 3.3 μM. Using human lung the IC50s were: 2.3 ± 1.3 μM for histamine; 0.3 ± 5.1 μM for leukotriene, and 0.3 ± 2.6 μM for thromboxane. CI-959 caused a concentration-dependent inhibition of anti-IgE-induced contractions of human bronchial muscle. Mean percent inhibitions were 45, 65 and 96 at 1, 3 and 10 μM, respectively. Cromolyn, 10 μM, inhibited bronchial contractions only 42%. The ability of CI-959 to inhibit these immunologically induced contractions indicates that the release of all mediators responsible for bronchoconstriction was effectively inhibited. These data suggest that CI-959 may be effective in preventing the development of symptoms directly related to inflammatory mediator release in a variety of allergic and inflammatory states.
Disodium Cromoglycate Inhibits Immunoglobulin Production in vitro without Affecting Cell Growth in Human B Cell Lines
Authors: Kimata Hajime , Yoshida Akira , Ishioka Chihiro , Mikawa Haruki
Published: August 2009

The effect of disodium cromoglycate (DSCG) on human B cell lines (IM-9, GM-1056, and AF-10) was studied. DSCG inhibited immunoglobulin production by these B cell lines without affecting thymidine uptake or cell number. Thus, in addition to its antiallergic function, DSCG may also act as a B cell-modulating reagent in vitro.
Presence of Autoantibody against Nasal Mucosal Cells in Patients with Wegener’s Granulomatosis
Authors: Kamitani Tetsu , Yuasa Kazumi , Mori Shigeo
Published: August 2009

We examined whether or not patients with Wegener’s granulomatosis have autoantibodies against the respiratory tract and kidney, by using the direct avidin-biotin-glucose oxidase complex method. On immunostaining, the IgG fractions obtained from the sera of 2 patients with Wegener’s granulomatosis and of 7 controls were coupled with biotin, and each couple was used as the primary antibody. The serum IgG sample from 1 patient with Wegener’s granulomatosis definitely reacted with epithelial cells of the nasal mucosa, with the strongest reaction in basal layer. The sample from another patient with Wegener’s granulomatosis showed a similar but weaker reaction. Control sera showed negative reactions in 6 subjects (3 with rheumatoid arthritis, 1 with allergic granulomatous angiitis and 2 normal volunteers) and a very weak reaction in 1 patient with polyarteritis nodosa. These observations suggest the presence of an autoantibody reacting with some cell components of the nasal epithelium in patients with Wegener’s granulomatosis.
Complement in Inflammation: Induction of Nephritides and Progress to Chronicity
Authors: Rother K. , Hänsch G.M. , Rauterberg E.W.
Published: August 2009

The C5b-9 complex has a dual role as a factor involved in the initiation of nephritides and in the progress to chronicity and sclerosis. The unique pathophysiology of the membrane attack complex, distinct from other mediators, is its independence from specific receptors. It inserted in any membrane lipid bilayer tested so far.
Ion Influx as a Transduction Signal in Mast Cells
Authors: Neher E.
Published: August 2009

Stimulation of mast cells leads to a transient increase in the concentration of free intracellular calcium, which, in a fraction of cells, is followed by a plateau of elevated calcium. The early part of this signal is due to release of calcium from intracellular stores. It is not important for secretion. The late plateau phase, if present, greatly accelerates secretion. It is mediated by two influx pathways, one of which can be identified as a nonspecific cationic channel.
Regulation of Airway Mucosal Ion Transport
Authors: Widdicombe J.H. , Kondo Mitsuko , Mochizuki Hiroyuki
Published: August 2009

The secretion of fluid into the airway lumen is due in part to active chloride secretion across the epithelium. Changes in Cl secretion require coordinated changes in the turnover of several transport proteins in order to avoid lethal changes in cell volume. Several different Ca- and cAMP-dependent pathways effect this coordination. Many mediators raise cyclic AMP which activates protein kinase A which in turn opens the apical membrane Cl channel. Cyclic AMP also raises Cai (without change in levels of inositol triphosphate, IP3), and this Ca is probably responsible for activation of basolateral K channels and NaK2Cl cotransporters. Other mediators raise Cai by elevating IP3, and seem to stimulate chloride secretion entirely by Ca-dependent pathways with no change in cyclic AMP levels. Protein kinase C and arachidonic acid inhibit Cl secretion.
Inhibitors of Protein and RNA Synthesis Block the Sensitization of Murine Peritoneal Mast Cells
Authors: Coleman J.W.
Published: August 2009

Addition of the protein synthesis inhibitor cycloheximide (CX, 1 μg/ml) and the RNA synthesis inhibitor actinomycin D (AD, 0.1 μg/ml) to unfractionated mouse peritoneal mast cells simultaneously with IgE anti-DNP, for 24 h prior to challenge, completely blocked antigen-induced 5-HT release. Responses to anti-IgE were strongly abrogated whereas responses to the calcium ionophore A23187 were not affected. When CX and AD were added to presensitized cells their effects on antigen and anti-IgE-induced release were much reduced. These results suggest a requirement for protein synthesis during mast cell sensitization.
Extracellular ATP Stimulates Interleukin-Dependent Cultured Mast Cells and Eosinophils through Calcium Mobilization
Authors: Saito H. , Ebisawa M. , Reason D.C. , Ohno K. , Kurihara K. , Sakaguchi N. , Ohgimi A. , Saito E. , Akasawa A. , Akimoto K. , Takatsu K. , Iikura Y.
Published: August 2009

We examined the effect of ATP and related nucleotides on the changes in intracellular calcium ([Ca2+]i) in murine bone marrow-derived mast cells (BMMC) and human cord blood-derived eosinophils (EO) cultured in the presence of interleukins. ATP, ADP and AMP released a substantial amount of histamine and leukotriene C4 from BMMC, and EO showed locomotive activity in response to ATP, ADP and GTP. These reactions were accompanied with an increase in [Ca2+]i in BMMC and in EO. The rise in [Ca2+]i in BMMC induced by ATP or antigen at optimal concentrations was inclined to be persisting. On the other hand, these nucleotides induced a rapid and transient rise in [Ca2+]i in EO. Purified human peripheral EO also exhibited locomotive activity and an increase in [Ca2+]i in response to ATP. These results indicate that extracellular ATP activates interleukin-dependent cultured mast cells and EO through Ca2+ mobilization, and suggest that ATP, which is known to be released from activated platelets or autonomic nerves, may stimulate in vivo counterparts of these cultured inflammatory cells.
Changes in Filament Actin Accompanying IgE-Dependent and -Independent Histamine Release from IL3-Dependent Cultured Human Basophils
Authors: Ebisawa M. , Saito H. , Reason D.C. , Sakaguchi N.S. , Katsunuma T. , Iikura Y.
Published: August 2009

When cord blood mononuclear cells were cultured in the presence of rhIL-3 for 5 weeks or more, 40–90% of cultured cells became morphologically mature basophils. We analyzed the kinetics of histamine release, changes in filament actin (F-actin), and movement of intracellular Ca2+ ([Ca2+]i) induced by IgE-dependent (anti-IgE) and -independent (fMLP) stimuli in these cultured basophils. Anti-IgE and fMLP released 24.5 ± 5.4% and 14.5 ± 4.5% histamine from the cells, respectively. Anti-IgE caused actin polymerization with a peak response at 15 min, which began much later than the elevation of [Ca2+]i. In contrast to anti-IgE stimulation, fMLP induced rapid actin polymerization with a peak response at 30 s in correlation with kinetics of histamine release. Our results indicate that cord blood-derived cultured basophils show similar cell functions to mature basophils, and are useful models with which to investigate the mechanisms of degranulation, specifically when a large amount of highly purified cells are required.
A GTP Analogue Induces Calcium Release but Not Secretion in Rat Mast Cells
Authors: von zur Mühlen Friederike , Penner Reinhold
Published: August 2009

Two G protein-mediated events, calcium release and secretion, were measured in single rat peritoneal mast cells using the patch-clamp technique. Various phosphorothioate analgoues of GTP were introduced into the cells. While GTPγS and Rp-GTPαS activated both processes, Rp-GTPβS was found to induce repetitive calcium release in the absence of exocytosis. This response was modulated by IP3, heparin, compound 48/80, and ATP. Our results suggest that Rp-GTPβS simulates Gp, which links receptors to calcium release.
New Concepts of IgE Regulation
Authors: Heusser Ch.H. , Bews J. , Brinkmann V. , Delespesse G. , Kilchherr E. , Ledermann F. , Le Gros G. , Wagner K.
Published: August 2009

B cell switch to IgE expression is mediated by IL-4 and is regarded as a T helper cell-related phenomenon. In this overview we describe that IgE switch can also be induced by mast cell/basophil like cells (from splenic non-B, non-T cells), activated by IgE receptor cross-linking and/or IL-3 which results in IL-4 production by these cells. Furthermore, activated mast cells produce their own growth factors, IL-3 and GM-CSF. Thus, activation of mast cells can provoke an ongoing local allergic reaction as long as antigen confrontation is maintained, a process which is sustained by further IgE production as well as renewal of mast cells. It is furthermore demonstrated that in certain established immune situations the IgE response may become independent of IL-4, namely in the spontaneous in vitro IgE expression of cells from atopic individuals as well as in an in vitro antigen-induced secondary IgE response of spleen cells derived from previously immunized mice. Thus, IgE-switched B cells may persist in vivo and may represent a pool of potentially IgE-producing cells. Finally, a selective inhibiton of the IgE response is described in vitro and in vivo by the use of so-called non-anaphylactic monoclonal anti-IgE antibodies. Such antibodies bind to surface IgE+ B cells, but not to IgE-sensitized mast cells, and thereby inhibit IgE responses. Nonanaphylactic antibodies blocked the binding of allergen-specific IgE to mast cells by competing with the Fcε on these cells. As a consequence they do not induce but rather prevent allergen-induced mediator release by mast cells. It is believed that corresponding antibodies to human IgE used in the chimeric (humanized) form will represent an attractive possibility to inhibit and/or eliminate IgE-switched B cells in vivo. This may lead to an efficient and isotype-specific suppression of human IgE responses.
Beta-2-Adrenoceptor Agonists Up-Regulate the in vitro FcEpsilon Receptor II/CD23 Expression on, and Release from, the Promonocytic Cell Line U937 and Human Blood Monocytes
Authors: Mencia-Huerta Jean Michel , Paul-Eugène Nathalie , Dugas Bernard , Petit-Frère Corinne , Gordon John , Lagente Vincent , Cairns Jennifer , Braquet Pierre
Published: August 2009

The possible regulatory role of β2-adrenoceptor agonists in the modulation of CD23 on the human promonocytic cell line U937 and on human monocytes was investigated. Incubation for 48 h in the presence of interleukin-4 (IL-4; 30 U/ml) induced optimal expression and release of CD23 on both U937 cells and human monocytes. When a β2-adrenoceptor agonist, either salbutamol or fenoterol, was added to U937 cells or monocytes both the IL-4-induced CD23 expression and release were markedly up-regulated. This effect was dose-dependent, starting at 10 nM and reaching a maximum at 1 μM final concentration of either salbutamol or fenoterol. The potentiating effect of salbutamol and fenoterol on CD23 expression and release was not observed when a β-adrenoceptor antagonist, either DL-propranolol (1 μM) or butoxamine (1 μM), was added to the incubation medium. The α-adrenoceptor agonist norepinephrine (1 μM) was ineffective in enhancing the IL-4-induced expression and release of CD23 from U937 cells or human monocytes, demonstrating the specificity of the β2-adrenoceptor-mediated effect. In the absence of IL-4, a moderate but significant increase in the CD23 expression on U937 cells and human monocytes by these drugs was observed, as compared to the basal values. These results indicate that, besides their bronchodilator effect, β2-adrenoceptor agonists may regulate IgE-dependent processes.
Are Allergen-Specific IgG Mainly IgG Anti-IgE Autoantibodies?
Authors: Jensen-Jarolim Erika , de Weck Alain L. , Stadler Beda M.
Published: August 2009

A large proportion of specific IgE occurred in immune complexes with anti-IgE autoantibodies in sera from nonhyposensitized allergic patients. These autoantibodies were misinterpreted as ‘specific IgG’ in different immunoassays such as dot immunoassays and the radioallergosorbent test (RAST), leading to overestimation of specific IgG. Purified immune complexes contained even more IgG than IgE antibodies. Heating of the complexes liberated specific IgE, producing an upwards RAST class shift. Thus anti-IgE autoantibodies are hiding the specific IgE, which is thereby underestimated. It is not known whether the hiding anti-IgE autoantibodies are also effectively neutralizing circulating or cell-bound IgE and might represent the actual blocking antibody.
Early Development of Mast Cells
Authors: Rottem Menachem , Kirshenbaum Arnold S. , Metcalfe Dean D.
Published: August 2009

Mast cells originate from pluripotential cells in the bone marrow. Specifically, human mast cells originate from CD 34-positive progenitor cells. Mast cell proliferation requires IL-3. In the mouse, additional mast cell growth is achieved by the addition of IL-4, and GM-CSF prevents mast cell proliferation. Early bone-marrow-derived mast cells can be identified by their IgE receptors, although they may not yet have the characteristic morphology of mature mast cells. Whether these early cells may by themselves have a physiologic role, remains to be determined. Mast cells persist in culture on fibroblast monolayers, in part due to the production of soluble factor(s) from the fibroblasts themselves. Final mast cell phenotype appears dependent upon the local tissue environment.
T-Cell-Dependent Accumulation of Eosinophils in the Lung and Its Inhibition by Monoclonal Anti-Interleukin-5
Authors: Okudaira Hirokazu , Nogami Makoto , Matsuzaki Go , Dohi Makoto , Suko Matsunobu , Kasuya Shiro , Takatsu Kiyoshi
Published: August 2009

The transnasal administration of an extract of the parasite Ascaris suum to C57BL/6 mice for 3 weeks produced marked eosinophilia in the bronchoalveolar lavage (BAL) fluid. The oral administration of ciclosporin significantly suppressed the pulmonary eosinophilia. Athymic C57BL/6-nu/nu mice failed to develop pulmonary eosinophilia. These data indicate that the pulmonary eosinophilia caused by this parasite extract is T-cell-dependent. Genetically mast-cell-deficient (WB × C57BL/6) F1W/Wv (W/Wv) mice developed marked eosinophilia in the BAL, which shows that mast cells are not necessary in the formation of lung eosinophilia in this model. Monoclonal antimurine interleukin-5 injected intraperitoneally clearly inhibited the infiltration of eosinophils in the lung, suggesting that T-cell-derived interleukin-5 is essential.