bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colony-stimulating factors and interferon-gamma differentially affect cell surface molecules shared by monocytes and neutrophils
Authors: BUCKLE A M , JAYARAM Y , HOGG N 
Published: July 2010

SUMMARYMonocytes and neutrophils share a common progenitor and perform many similar functions, as reflected in the expression of several shared membrane molecules. We show here that such molecules can be independently regulated by the cytokines interferon-gamma (IFN-γ) and the colony-stimulating factors (CSF) in the context of the cell type on which they are present. Thus, IFN-γ causes neutrophils to express the high-affinity receptor for IgG, FcγRI, which has been considered to be a monocyte-specific receptor. Although neutrophil FcγRI never reaches the levels present on monocytes. it is induced more rapidly and by lower amounts of IFN-γ than monocyte FcγRI. Of the CSF, only macrophage (M) CSF has an effect which is to cause a decrease in expression of monocyte FcγRI. Secondly, after culture monocytes express FcγRIII which is constitutively expressed by neutrophils. Although ncutrophil FcγRIII can be readily modulated by IFN-γ. granulocyte (G) CSF and granulocyte macrophage (GM) CSF, these cytokines do not alter the low levels of monocyte FcγRIII. Thirdly, expression of the gp55 protein recognized by CD14 monoclonal antibodies is decreased after exposure of monocytes to IFN-γ. Neutrophils express low levels of CD14 and, in this case. IFN-γ causes an increase in the CD 14 antigen on these cells. Of all the molecules investigated, only HLA class II is confined to monocytes. with increases in expression induced by IFN-γ but not by the CSF.
The neuropeptide substance P stimulates the effector functions of platelets
Authors: DAMONNEVILLE M , MONTÉ D , AURIAULT C , CAPRON A 
Published: July 2010

SUMMARYSensory neuropeptides, such as substance P. appear as potent mediators of various immunological reactions, and inhibit or stimulate a wide range of functions of immune inflammatory cells. Platelets were recently shown to participate as effector cells in an IgE or lymphokine-dependent killing of parasites. Substance P and its carboxy-terminal fragment SP (4–11) induce the cytotoxic activity of platelets towards the larvae of Schistosoma mansoni, respectively, by 90% and 40%, whereas the modified C terminal SP, the SP-free acid, exhibits no effect on the platelets. The neuropeptide effects occur at low doses (10-8 M), are specific as shown by inhibition studies with a substance P antagonist, theD-SP. Binding data obtained after flow cytofluorometry with FITC-SP lead to the conclusion that SP binds specifically to about 20% of the homogenous population of platelets. Moreover, IgE could modulate the SP-dependent functions of platelets since the pre-incubation with myeloma human IgE or with AP2 monoclonal antibodies—known to inhibit the IgE-dependent killing of these cells leads to a dramatic decrease of the SP dependent cytotoxic activity of platelets towards the larvae. These findings identify a potent mechanism for nervous system regulation of host defence responses.
Relative increase of inflammatory CD4+ T cells in the cerebrospinal fluid of multiple sclerosis patients and control individuals
Authors: ROTTEVEEL F T M , KUENEN B , KOKKELINK I , MEAGER A , LUCAS C J 
Published: July 2010

SUMMARYOf three patients with multiple sclerosis (MS) and two non-MS individuals a large number of CD4+ T cell clones was obtained from the cerebrospinal fluid and peripheral blood by direct limiting dilution. The CD4+ T cell clones from cerebrospinal fluid and peripheral blood lymphocytes were compared for their cytotoxic activity and lymphokine production. Cytotoxic capacity of cloned T cells was analysed with the use of anti-CD3 antibodies and target cells bearing Fc receptors for murine IgG. Recently, we demonstrated the existence of two different subsets of human CD4+ T cell clones by phenotypic and functional criteria. One type of CD4+ T cell with anti-CD3 mediated cytotoxic activity, in analogy with murine studies, is the inflammatory or TH1 subtype, the main producer of interleukin (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor (TNF)-α, -β, whereas the other type of CD4+ T cell clone lacked anti-CD3 mediated cytotoxicity and produced minimal amounts of IL-2 concomitant with reduced levels of IFN-γ and TNF-α, -β. The present study demonstrates that among three MS patients, relatively more inflammatory CD4+ T cell clones with cytotoxic activity and IFN-γ and TNF-α, -β production were derived from the cerebrospinal fluid as compared with peripheral blood lymphocytes. Also among control individuals more inflammatory CD4+ T cell clones could be obtained from the cerebrospinal fluid as from the peripheral blood. The enrichment of inflammatory CD4+ T cells, therefore, appears to be physiological rather than associated with the disease.
Anti-endothelial cell antibodies in patients withWegener's granulomatosis and micropolyarteritis
Authors: FERRARO G , MERONI P L , TINCANI A , SINICO A , BARCELLINI W , RADICE A , GREGORINI G , FROLDI M , BORGHI M O , BALESTRIERI G 
Published: July 2010

SUMMARYAnti-endothelial cell antibodies (AECA) have been detected by cell surface radioimmunoassay innine out of 15 patients with micropolyarteritis (MPA) and in two out of five patients with Wegener'sgranulomatosis. AECA mostly belonged to the IgG isotype and were present in the active phase ofthe diseases. These antibodies were not detectable in 10 sera from patients with essential mixedcryoglobulinaemia. suggesting that they were not a mere epiphenomenon consequent to theinflammatory vascular injury. The binding activity was not related to ABH antigens or to HLA class Iantigens displayed by resting human endothelial cells in culture and was not influenced by removingimmune complexes. Absorption of the anti-neutrophil cytoplasmic antibodies (ANCA). present inMPA and Wegener's granulomatosis sera, did not affect the endothelial binding. AECA-positive seradid not display lytic activity against endothelial cells, neither alone nor after addition of freshcomplement or normal human peripheral blood mononuelear cells. Although AECA arc notcytolytic for endothelial cell monolayers in vitro, the reactivity against intact endothelial cells suggeststheir possible involvement in in vivo pathological processes affecting vascular structures in smallvessel primary vasculitides.
The affinity of anti-HBc antibodies in acute and chronichepatitis B infection
Authors: WEN Y M , DUAN S C , HOWARD C R , FREW A F , STEWARD M W 
Published: July 2010

SUMMARYAntibodies to hepatitis B core antigen (anti-HBc) are found in the sera of all individuals infected withhepatitis B virus. A role for these antibodies has been suggested in determining the outcome ofinfection. In this study, the affinity of anti-HBc antibodies in asymptomatic virus carriers wascompared with that of antibodies present in the sera of patients with chronic liver disease. Persistentlyinfected individuals with no evidence of clinical disease were found to have anti-HBc antibodies ofgreater affinity, compared with the chronic liver disease group. Sera from patients with chronichepatitis contained high levels of low-affinity antibody whereas antibody levels in asymptomaticcarriers were significantly lower. These findings are discussed in relation to the predicted role of anti-HBc antibodies in mediating hepatitis B virus-related hepatocellular injury.
Complement activation and the prognostic value of C3a in patients at risk of adult respiratory distress syndrome
Authors: ZILOW G , STURM J A , ROTHER U , KIRSCHFINK M 
Published: July 2010

SUMMARY
In vivo and in vitro studies have shown that complement activation plays an important role in the pathogenesis of the adult respiratory distress syndrome (ARDS). In a prospective study of polytrauma patients at risk of ARDS (n= 38) complement parameters were determined over a period of 14 days in serial plasma samples (obtained every 6 h during the first 48 h). Polytrauma induced a rapid and remarkable complement activation. Low levels of the complement proteins C3, C4, C1 inhibitor (Cl INH) factor I and factor H during the first 48 h indicated complement consumption in all patients. Elevated C3a levels in the first few hours after injury were associated with the later development of ARDS. A more sensitive indicator than C3a alone was the calculated C3a:C3 ratio discriminating ARDS and non-ARDS patients. A second rise of C3a levels and C3a:C3 ratio from day 4 on paralleled the course of extravascular lung water. To assess the mode of complement activation, the activation-specific protein complexes Cl rCls-Cl INH and C3b(Bb)P were measured in some of the patients. We demonstrate that in the first 48 h complement activation occurred via the alternative pathway only and was later followed by an additional activation via the classical pathway. Our observations suggest that monitoring of C3a and C3 in plasma can identify polytrauma patients at high risk for ARDS at an early stage of the disease.
Thyroid peroxidase and the induction of autoimmune thyroid disease
Authors: MCLACHLAN S M , ATHERTON M C , NAKAJIMA Y , NAPIER J , JORDAN R K , CLARK F , SMITH B REES 
Published: July 2010

SUMMARYAnimal models of autoimmune thyroid disease are associated with thyroglobulin (Tg) as autoantigen whereas in man the autoimmune response to microsomal antigen/thyroid peroxidase (TPO) appears to play a major role in thyroiditis. Consequently, we have compared the ability of TPO and Tg to induce thyroid autoantibodies and thyroid damage in mice known to be susceptible (CBA/J) or resistant (BALB/c) to thyroiditis induced using murine Tg. Groups of three to five mice were immunized twice using Freund's complete adjuvant with 80–100μg highly purified porcine (p) TPO, pTg, rat (r) Tg, human Tg, bovine serum albumin (BSA) or BSA + 0.2 μg pTg (the level of Tg contamination of TPO). Four weeks after immunization with TPO, plasma from CBA/J (but not BALB/c) mice contained IgG class antibodies which bound to TPO-coated tubes in the presence or absence of excess Tg (and could therefore be clearly distinguished from Tg antibodies) but there was no evidence of thyroiditis in either strain of mice. In contrast, in CBA/J mice immunized with rTg and, to a lesser extent in mice that had received pTg, thyroid tissue was infiltrated with lymphoid cells and/or neutrophils and antibodies to pTg (but not pTPO) were present. Our observations demonstrate that induction of TPO antibody alone is insufficient to lead to thyroiditis in CBA/J mice. Further, these studies emphasize the complex interactions between MHC and different thyroid antigens in the processes leading to thyroid destruction.
Mechanism of a lymphocyte abnormality associated with HLA-B8/DR3: role of interleukin-1
Authors: HASHIMOTO S , MICHALSKI J P , BERMAN M A , MCCOMBS C 
Published: July 2010

SUMMARYLymphocytes from normal individuals with the histocompatibility antigens HLA-B8 and DR3 have impaired proliferative responses when stimulated with suboptimal concentrations of mitogens. We have previously shown that an important factor in the impaired response is a failure to produce normal quantities of interleukin-2 (IL-2). To examine the mechanism of decreased responsiveness further, we measured interleukin-1 (IL-1) production of low responder subjects compared with controls. The peripheral blood mononuelear cells of five low responder individuals with HLA-B8/ DR3 stimulated with 0.05 μg/ml of phytohaemagglutinin (PHA) accumulated only 0.036 U/ml of IL-I compared with 0.32 U/ml for normal respondcrs. There was a highly significant correlation between the PHA-stimulated IL-1 concentration at 12 h and the subsequent IL-2 concentration at 48 h (r=0.89, P&lt;0.000l) suggesting a role of decreased IL-1 production in the impaired response. A study of unfractionated or column-fractionated culture supernatants revealed no evidence that the decreased IL-1 activity in the supernatants of low responder subjects was related to increased IL-1 inhibitor concentrations. These results suggest that impaired IL-2 production and lymphocyte proliferation in healthy subjects with HLA-B8/DR3 may be mediated at least in part by decreased IL-1 production, and implicates a defect of a very early event in lymphocyte activation.
Effects of a novel immunosuppressive agent, FK506, on human B cell activation
Authors: SUZUKI N , SAKANE T , TSUNEMATSU T 
Published: July 2010

SUMMARYWe examined the effect of new immunosuppressive agent, FK506, on the human B cell function, in comparison with that of cyclosporin A (CyA) and tried to define the discrete activation step(s) which is selectively affected by FK506 and CyA. We used polyclonal B cell activators, Staphylococcus aureus Cowan I (SAC) and pokeweed mitogen (PWM). We found that (i) the initial B cell activation process by PWM, which is on the basis of T cell-dependent manner, is susceptible to the inhibitory effects of FK506 and CyA. while initial B cell activation on the basis of T cell-independent manner by SAC is resistant to these drugs: (ii) they also inhibit helper factor production by T cells; (iii) once they are activated, the B cells become resistant to inhibition by the drugs; and (iv) on an equimolar basis, FK506 exhibits 100-fold greater inhibitory activity than does CyA. Thus FK506 mainly interferes with interactions between T cells and other cells which are essential for B cell activation process, resulting in inhibition of B cell function.
Loss of natural killer activity as an indicator of relapse in acute leukaemia
Authors: TRATKIEWICZ J A , SZER J 
Published: July 2010

SUMMARYA role for naturally occurring cytotoxic cells in immunosurveillance against malignancy has been presumed in several studies. The natural killer activity (NKA) of peripheral blood mononuclear cells was therefore measured at regular intervals in patients with acute leukaemia and expressed specific cytotoxicity. Sixty controls had a median NKA of 33·6% (range 15·4–71). Seventy-three patients with acute lymphoblastic leukaemia (ALL) and acute non-lymphoblastic leukaemia (ANLL) with untreated or relapsed disease had a median activity of 2·4% (range 0–13·4) (P&lt; 0·001), while 57 patients who had achieved complete remission had a median activity of 22·7% (range 9·5–64·4). In 15 patients, reductions of NKA were seen prior to 16 episodes of relapse. In ten of these (nine with ANLL and one with ALL), 11 relapses were preceded within 10 weeks by drops in NKA to less than 30% of remission levels. The median NKA of the group prior to the drop in activity was 25·5% and the median first low value was 60%. Five patients who relapsed after allogeneic bone marrow transplantation had significant, sustained drops in NKA, 5–9 weeks earlier. The median NKA prior to the drop was 25·6% and the median first low value was 8·0%. We therefore conclude that there was a marked reduction in NKA in patients with active acute leukaemia when compared with healthy blood donors and that this activity substantially improved in complete remission. All patients who relapsed had significantly reduced NKA which in some, significantly preceded the time of relapse. These data suggest that the regular assessment of NKA in patients with acute leukaemia may be a useful diagnostic tool.
Murine monoclonal antibodies to DNA. A comparison of MRL/lpr NZB/W and chronically graft-versus-host-diseased mice
Authors: BRINKMAN K , VAN DAM A , VAN DEN BRINK H , TERMAAT R-M , BERDEN J , SMEENK R 
Published: July 2010

SUMMARYHybridomas producing monoclonal antibodies to DNA were prepared from NZB/W F1 (n= 20), MRL/lpr (n= 13), mice with a chronical graft versus-host-disease (GVHD) (n= 8) and polyclonally stimulated mice (n = 9). Screening was performed by means of an anti-DNA EL1SA. Reaction patterns in four different anti-DNA assays (anti-DNA ELISA, indirect immunofluorescence on Crithidia luciliae. PEG assay and Farr assay) as well as avidity and cross-reactivity of these monoclonals were studied in relation to anti-DNA (sub)class and murine origin of the clones. It was found that monoclonal anti-DNA derived from mice with chronic GVHD did not differ from monoclonal anti-DNA derived from NZB/W Fl or MRL/lpr mice, with respect to isotype distribution, avidity towards DNA, cross-reactivity and assay behaviour in the anti-DNA assays mentioned before. In contrast, monoclonal anti-DNA obtained from polyclonally stimulated mice were all of the IgM isotype and displayed a stronger cross-reactive behaviour than the other three models. Altogether, these results exclude the possibility that anti-DNA in the GVHD mice originates from the non-specific pool of natural autoantibodies and further emphasize the relevance of chronic GVHD as a murine model of systemic lupus erythematosus.
Immunomodulation in mineral dust-exposed lungs: stimulatory effect and interleukin-1 release by neutrophils from quartz-elicited alveolitis
Authors: KUSAKA Y , CULLEN R T , DONALDSON K 
Published: July 2010

SUMMARYQuartz deposition in the rat lung causes an intense and persistent neutrophil alveolitis leading to parenchy mal fibrosis. Bronchoalveolar leucocytes (BAL) from quartz-exposed rat lungs were studied for their effects on splenic lymphocyte proliferation; titanium dioxide (TiO2) was used as a control, non-fibrogenic dust. Seven days after the intratracheal instillation of 1 mg of quartz or TiO2 suspended in phosphate-buffered saline (PBS), BAL were recovered by lavage; the effect of PBS alone was also studied. TiO2-elicited BAL (macrophages &gt; 98%) inhibited splenocytes responding to suboptimal phytohaemagglutinin (PHA) more than PBS-elicited BAL (macrophages &gt; 98%); the effect was dependent on the BAL:splenic lymphocyte ratio. Quartz-elicited whole BAL (macrophages 49%, neutrophils 51 %), and an alveolar macrophagc-enriched population with purity of 87% separated from it, were less inhibitory to splenocyte mitogenesis than PBS-elicited BAL. A neutrophil-enriched population, with a purity of 80%, markedly enhanced splenocyte response to PHA. In addition, whole quartz BAL and the macrophagc-enriched population obtained from it enhanced the mitogenesis of T cell-enriched lymphocytes at a much lower BAL:lymphocyte ratio. The neutrophil-enriched quartz BAL enhanced mitogenesis substantially more than the whole or macrophage-enriched population from quartz-exposed lung. Supernatants from normal macrophages, PBS BAL, TiO2 BAL, quartz BAL and both alveolar macrophage and neutrophil-enriched quartz populations were assessed for interleukin-1 (IL-1) activity. Quartz-BAL, quartz macrophages and quartz neutrophils all produced significantly higher IL-1 levels than PBS BAL; the supematants from quartz neutrophils, however, showed the highest IL-1 activity. These findings suggest that quartz-elicited bronchoalveolar leukocytes, especially neutrophils, enhance lymphocyte proliferation and that increased IL-1 secretion by these cells is likely to be the effector molecule involved. These findings have important implications for immune response in mineral dust-stimulated lung and for inflammatory lung disease in general.
Specificities of IgM and IgG anti-histone H1 autoantibodies in autoimmune mice
Authors: MONESTIER M , FASY T M , DEBBAS M E , BOHM L 
Published: July 2010

SUMMARYAutoantibodies to histone H1 represent the most common specificity among anti-histone autoantibodies in systemic autoimmune diseases. Here we analyse anti-H1 autoantibodies in mice from the following autoimmune strains: MRL/Mp-lpr/Ipr. NZB and NZB × NZW/F1. Autoantibodies of the IgM isotype bind predominantly to epitopes located in the COOH-terminal domain of the H1 molecule, whereas IgG autoantibodies in the MRL/Mp-lpr/Ipr and NZB strains also recognize epitopes requiring the integrity of both the COOH-terminal and the central globular domains of H1. In both of these strains, the titre of these IgG anti-H 1 antibodies rises during the course of the disease. The importance of three-dimensional structure of histone H1 was attested by a significant decrease in IgG binding after cleavage of the H1 molecule within the folded globular domain. The binding of these sera to H1 variants from various species was also investigated and a strong binding of MRL/Mp-lpr/lpr sera to certain phylogenetically distant histone H1 variant molecules (sea-urchin sperm H1 and chicken erythrocyte H5) was observed. This cross-reacting binding can be explained by the presence in MRL/Mp-lpr/lpr sera of autoantibodies to H10, a variant found in non-dividing cells and exhibiting sequence homologies lo the above mentioned variants. The significance and the possible implications of these data for the pathogenesis of autoimmunity are discussed.
Anti-M9 antibodies in sera from patients with primary biliary cirrhosis recognize an epitope of glycogen phosphorylase
Authors: KLEIN R , BERG P A 
Published: July 2010

SUMMARY
Anli-M9 antibodies in sera from patients with primary biliary cirrhosis (PBC) were previously found to recognize two antigenic determinants at 98 and 59 kD, using a purified antigen fraction derived from rat liver mitochondria in the Western blot. Here we show that these antibodies are directed against an epitope of the enzyme glycogen phosphorylase. By Western blotting, a determinant at 98 kD was obtained testing anti-M9 positive sera against phosphorylase from skeletal muscle, and after plasmin treatment a degradation product appeared at 59 kD. Both determinants were identical to the M9-specific determinants 98 and 59 kD as shown by absorption studies. When these antibodies were eluted from the 98 and 59 kD determinants of the M9 antigen after immunoblotting. they again recognized the same epitopes on plasmin-treated phosphorylase. Furthermore, phosphorylase enzyme activity could be also demonstrated in the purified M9 fraction, and anti-M9-positive/anti-M2-negative but not anti-M9-negative/anti-M2-positive sera could be shown to stimulate phosphorylase activity. Testing sera from 1189 patients with different hepatic and non-hepatic disorders against M9 and phosphorylase from skeletal muscle by ELISA. 20% were positive with phosphorylase and only 2% with the M9 fraction. These data indicate that the commercially available phosphorylase from skeletal muscle cannot be recommended as M9 source. It may still contain non-PBC-specific epitopes which are probably recognized by naturally occurring antibodies directed against this highly conserved protein.
Kinetics and pathogenicity of autoantibodies induced by mercuric chloride in the brown Norway rat
Authors: PUSEY C D , BOWMAN C , MORGAN A , WEETMAN A P , HARTLEY B , LOCKWOOD C M 
Published: July 2010

SUMMARYRepeated low-dose injections of mercuric chloride (HgCl2) in the brown Norway (BN) rat result in polyclonal activation which includes the induction of anti-glomerular basement membrane (GBM) autoantibodies. We examined the kinetics of various auloantibodies produced in vivo, general features of polyclonal activation such as total IgG levels and immune complex formation, and the relationship between organ specific autoimmunity and tissue injury in the kidney and thyroid. The production of immune complexes and autoanlibodies to GBM and thyroglobulin was short lived, and the increase in levels of total IgG and antibodies to ssDNA and dsDNA was prolonged; the antibody response to collagen types I and II was intermediate in duration. Auloantibodies induced by HgCI2 caused only mild and variable tissue injury in the kidneys and did not induce abnormalities in the thyroid. These studies demonstrate that immunostimulation by mercury may result in the formation of a range of autoantibodies. with variable kinetics and pathogenicity.