bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of macrophage inflammatory protein (MIP)-1α, MIP-1β, and RANTES genes in lymph nodes from HIV+ individuals: correlation with a Th1-type cytokine response
Authors: Trumpfheller C , Tenner-Racz K , Racz P , Fleischer B , Frosch S 
Published: March 2003

SUMMARYThe in vivo response of the immune system after HIV infection in regard to cytokine production and C-C chemokine synthesis is not well known. Here we have analysed cytokine and chemokine mRNA production in lymph nodes with follicular hyperplasia (FHLN) of HIV-infected patients by in situ hybridization using anti-sense mRNA probes. The synthesis of mRNAs for interferon-gamma (IFN-γ), IL-12p35, IL-12p40, IL-4, and for the C-C chemokines RANTES, MIP-1α, and MIP-1β was compared with that of lymph nodes from non-infected individuals to define HIV-specific events. Only few cells expressing IFN-γ, RANTES, MIP-1α, and MIP-1β mRNAs were detectable in the T-dependent area of lymph nodes from HIV-negatives. In contrast, in FHLN from HIV+ patients a high number of IFN-γ, RANTES, MIP-1α, and MIP-1β mRNA-containing cells were detectable. Remarkably, only single individual IL-12p35 mRNA-producing cells were present in the T-dependent area from both HIV+ and HIV− lymph nodes. Furthermore, the low number of IL-12p40 mRNA-expressing cells did not differ between HIV+ and HIV− lymph nodes. This indicates that IFN-γ is expressed independently of IL-12, possibly by a direct T cell-mediated reaction. IL-4 mRNA-producing cells were hardly detectable in infected and control lymph nodes. The same findings were made in a limited number of samples from patients with advanced disease. Thus, these results demonstrate that a high IFN-γ production is accompanied by a strong expression of MIP-1α, MIP-1β, and RANTES in the lymph node after HIV infection. This favours the idea that a Th1-type immune response correlates with a preferential production of C-C chemokines in FHLN of HIV+ patients.
The human autoantigen La/SS-B accelerates herpes simplex virus type 1 replication in transfected mouse 3T3 cells
Authors: Bachmann M , Deister H , Pautz A , Laubinger J , Schmitz M , Falke D , Podlech J , GRölz D 
Published: March 2003

SUMMARY
Permanently transfected mouse cell lines which expressed different levels of the human autoantigen La/SS-B were infected with different strains of herpes simplex virus type 1, including the strains ANG, HSZP, 17syn+ and HFEM. During infection the localization of the human La protein was followed using an anti-La MoAb, which recognized only the human La protein but did not cross-react with either the endogenous mouse La protein or any viral encoded protein. After infection La protein was transported from the nucleus to the cytoplasm. The time course of translocation was dependent on the amount of human La protein expressed in the respective cell line. Moreover, acceleration of viral replication was dependent on the level of expression of human La protein, suggesting that La protein is a cellular factor that facilitates virus replication.
Autoimmunity to tropomyosin isoforms in ulcerative colitis (UC) patients and unaffected relatives
Authors: Biancone L , Monteleone G , Marasco R , Pallone F 
Published: March 2003

SUMMARYAutoimmunity to cytoskeletal protein tropomyosin (TM) has been demonstrated in UC. However, the TM isoforms involved in this IgG-mediated autoimmune response in UC and the possible presence of serum IgG antibodies against TM (hTMs IgG) in unaffected UC relatives are unknown. The aim of this study was to investigate the human TM (hTM) isoforms recognized by serum IgG from UC and to explore whether hTM IgG antibodies are present in healthy UC relatives. We studied 33 UC patients with 58 unaffected relatives, 31 Crohn's disease (CD) patients with 31 unaffected relatives and 20 controls (C). Serum IgG against four recombinant hTM isoforms (hTM1, 2, 3, 5) were tested by ELISA. p-ANCA were tested by ELISA and immunofluorescence. Serum hTM1 and hTM5 IgG were higher in UC patients than in CD and C (P &lt; 0.005). Among UC patients 52% were seropositive for hTM1 and 64% for hTM5 (P &lt; 0.001 versus CD and C). In UC, hTM5 IgG were higher in p-ANCA+ than in ANCA− patients (P = 0.04). In UC relatives hTM1 IgG were higher than in CD relatives and C (P &lt; 0.01). UC relatives were more frequently seropositive for hTM1 than hTM5 IgG (P = 0.001), while probands were more frequently seropositive for hTM5 IgG (P = 0.008). We conclude that autoimmunity to hTM1 and hTM5 is a feature of UC, while hTM1 IgG differentiate UC relatives from controls. A genetic susceptibility to immune recognition of hTM isoforms in UC is suggested.
Stimulation with thromboxane A2 (TXA2) receptor agonist enhances ICAM-1, VCAM-1 or ELAM-1 expression by human vascular endothelial cells
Authors: Ishizuka T , Kawakami M , Hidaka T , Matsuki Y , Takamizawa M , Suzuki K , Kurita A , Nakamura H 
Published: March 2003

SUMMARYA previous study reported that intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells (HUVEC) is augmented by intracellular signal transmission mainly through the protein kinase C (PKC) system stimulated by TXA2 receptors. In the present study, we show that a TXA2 receptor agonist, U46619, augments the expression of not only ICAM-1, but also vascular cell adhesion molecule-1 (VCAM-1) or endothelial leucocyte adhesion molecule-1 (ELAM-1) in HUVEC both at protein and mRNA levels. Pretreatment with SQ29,548 (a TXA2 receptor antagonist) or PKC inhibitors greatly diminished the extent of U46619-induced mRNA accumulation and surface expression of the adhesion molecules. An inhibitor of nuclear factor κB (NF-κB) activation, PDTC, diminishes U46619-induced VCAM-1 mRNA accumulation. NAC, which inhibits NF-κB and activation protein 1 (AP-1) binding activity, inhibits the expression of ICAM-1 or ELAM-1 at protein and mRNA levels. These findings suggest that ICAM-1 or ELAM-1 expression of HUVEC stimulated via TXA2 receptors is augmented by induction of NF-κB and AP-1 binding activity through the PKC system, and that VCAM-1 expression is augmented by induction of NF-κB binding activity.
Humoral immune response to mycobacterial heat shock protein (hsp)65 in the cerebrospinal fluid of neuro-Behçet patients
Authors: Taşçi B , Direskeneli H , Serdaroğlu P , Akman-Demir G , Eraksoy M , Saruhan-Direskeneli G 
Published: March 2003

AbstractAlthough systemic immune reactivity to 65-kD mycobacterial hsp65 (m-hsp65) has been shown previously in Behçet's disease (BD), local immune response was not investigated. We studied anti-m-hsp65 IgG, IgM and IgA antibodies in the serum and cerebrospinal fluid (CSF) of 25 BD patients with cerebral parenchymal involvement (p-NBD), seven BD patients with intracranial hypertension (ih-NBD), eight BD patients without central nervous system (CNS) involvement, 30 patients with multiple sclerosis (MS) and 24 patients with non-inflammatory CNS disorders (NIC). Significantly higher CSF IgG responses were detected in p-NBD patients (ELISA ratio 1.3 ± 0.9) compared with NIC (0.7 ± 0.4, P &lt; 0.01). In p-NBD patients' IgG, IgM or IgA CSF anti-m-hsp65 positivity rate was 48% (12/25); this was significantly higher when compared with MS (3/30; P &lt; 0.03) and NIC (3/24; P &lt; 0.01). CSF anti-m-hsp65 IgG ratios correlated with the duration of BD (r = 0.4, P &lt; 0.04) but not with the duration of neurological involvement. Serum IgM and IgA responses were elevated in ih-NBD, suggesting a different type of involvement than p-NBD. These results implicate an increased local humoral response to m-hsp65 in the CSF of p-NBD patients, which might be related to the pathogenesis of neurological involvement.
Immune complex-like moieties in immunoglobulin for intravenous use (IVIg) bind complement and enhance phagocytosis of human erythrocytes
Authors: Shoham-Kessary H , Naot Y , Gershon H 
Published: March 2003

AbstractTreatment with IVIg can, on rare occasions, lead to detrimental effects such as enhanced erythrocyte sequestration and an increase in serum immune complexes with inflammatory sequellae such as exacerbation of glomerular nephritis. In this study, IVIg (Sandoglobin) was examined for complement binding moieties which resemble immune complexes and can mediate the binding of IgG and C′3b to human erythrocytes via CR1 and enhance erythrocyte susceptibility to sequestration. Sephacryl S-200 HR separated IVIg into two fractions: monomeric IgG (74%) and larger complexes of the molecular weight of an IgG dimer or greater (≥ 300 kD) (26%). In the presence of complement, the ‘dimers’ bound to human erythrocytes, rendering them susceptible to phagocytosis in vitro. Removal of erythrocyte-specific isoantibodies from the IVIg had no effect on ‘dimer’ binding to the erythrocytes. Monomeric IgG contained virtually no complement-activating, erythrocyte-binding activity. Erythrocyte binding of complement-bearing IgG ‘dimers’ and subsequent phagocytosis resembles the binding of complement-bearing immune complexes to erythrocyte CR1. Exposure to Factor I leads to the release of complement-bearing IgG ‘dimers’ from erythrocyte CR1 and to the abrogation of erythrophagocytosis. Binding of complement-bearing IgG ‘dimers’ to the erythrocyte is blocked by To5, a CR1-specific monoclonal antibody.
Increased spontaneous apoptosis in T lymphocytes in DiGeorge anomaly
Authors: Gupta S , Aggarwal S , Nguyen T 
Published: March 2003

AbstractThe aim of this study was to determine whether increased apoptosis in peripheral blood lymphocytes plays a role in T cell deficiency associated with DiGeorge anomaly. T cell subsets from a patient with DiGeorge anomaly were examined for the expression of Fas, FasL, Bcl-2 and Bcl-XL at the protein level with monoclonal antibodies, using dual-colour flow cytometry, and at the mRNA level in mononuclear cells by quantitative reverse transcriptase-polymerase chain reaction. In vitro spontaneous apoptosis was examined by propidium iodide staining and DNA fragmentation, using flow cytometry and gel electrophoresis, respectively. Fas and FasL expression, both at the level of protein and of mRNA, was increased, whereas Bcl-2 expression was decreased both at the level of protein and of mRNA. However, no difference in Bcl-XL expression was observed between the patient and an age-matched control. A significant proportion of both CD4+ and CD8+ T cells from the patients underwent spontaneous apoptosis, whereas almost no spontaneous apoptosis was observed in the age-matched control. These data suggest that spontaneous apoptosis in T lymphocytes, at least in part, may be responsible for T cell deficiency in DiGeorge anomaly.
Characteristics ofPrevotella intermedia-specific CD4+ T cell clones from peripheral blood of a chronic adult periodontitis patient
Authors: Wassenaar A , Reinhardus C , Abraham-Inpijn L , Snijders A , Kievits F 
Published: March 2003

AbstractPeriodontitis is a chronic destructive inflammatory disease associated with periodontopathic bacteria. In addition, autoantigens such as collagen and heat shock proteins (hsp) have been suggested to play a role. Established periodontal lesions are characterized by dense infiltrations of immune cells such as cytokine-producing CD4+ and CD8+ T cells. CD4+ T cells specific for Prevotella intermedia can be isolated from lesional gingiva, suggesting an active role for CD4+ T cells in the response to this bacterium. We therefore investigated the characteristics of a panel of 13 P. intermedia-specific CD4+ T cells generated from the peripheral blood of a patient with chronic adult periodontitis. All 13 P. intermedia-specific CD4+ T cells recognized the antigens in the context of HLA-DR. The T cell clones were mainly classified as Th0, producing comparable amounts of interferon-gamma (IFN-γ) and IL-4, and Th2, producing high amounts of IL-4 and almost no IFN-γ. None of the P. intermedia-specific T cell clones recognized antigens of the periodontopathic bacteria Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis and of the autoantigens collagen and hsp. The reactivity profile of the T cell clones to size-fractionated cell envelope antigens of P. intermedia indicated that P. intermedia-specific CD4+ T cell clones recognize probably five different antigen specificities in the context of the MHC class II molecules, DR7 or DR15. These results suggest that a broad panel of cell-associated protein antigens play a role in the induction of P. intermedia-specific CD4+ T cell response.
IL-10 up-regulates nitric oxide (NO) synthesis by lipopolysaccharide (LPS)-activated macrophages: improved control ofTrypanosoma cruziinfection
Authors: Jacobs F , Chaussabel D , Truyens C , Leclerq V , Carlier Y , Goldman M , Vray B 
Published: March 2003

AbstractWe examined the effects of IL-10 on tumour necrosis factor-alpha (TNF-α) and NO production by LPS-activated macrophages and on the ability of these cells to control Trypanosoma cruzi infection. We first observed that the addition of rIL-10 to macrophages of the J774 cell line decreased their synthesis of TNF-α but increased their release of NO in a dose-dependent manner. In parallel, treatment of J774 cells with rIL-10 resulted in a better control of T. cruzi infection involving up-regulation of NO synthesis, as it was not observed in presence of N-nitro- l-arginine methyl ester (l-NAME), a competitive inhibitor of NO synthase. The enhancing effect of rIL-10 on NO production was not observed on peritoneal macrophages from wild-type C57Bl/6 mice, but well on macrophages from IL-10 knock-out mice. The control of NO production by endogenous IL-10 was confirmed by the demonstration that neutralization of IL-10 secreted by LPS-activated macrophages from wild-type mice inhibited their production of NO and, in parallel, their ability to control T. cruzi infection. Taken together, these data demonstrate that both exogenous and endogenous IL-10 up-regulate the production of NO by LPS-activated macrophages and improve thereby their ability to clear T. cruzi infection.
Cytokine expression in squamous intraepithelial lesions of the uterine cervix: implications for the generation of local immunosuppression
Authors: Giannini S L , Al-Saleh W , Piron H , Jacobs N , Doyen J , Boniver J , Delvenne P 
Published: March 2003

SUMMARYWe have addressed the notion that the progression of cancer of the uterine cervix is associated with a preferential constraint on the development of a type 1 cellular mediated response, which is necessary to efficiently eliminate (pre)neoplastic cells. Based on the importance of cytokines in the regulation of an appropriate immune response, we have evaluated the expression of IL-12p40, IL-10 and transforming growth factor-beta 1 (TGF-β1). Using reverse transcriptase-polymerase chain reaction (RT-PCR), the expression of these three cytokines was evaluated in both low-grade (LG) and high-grade (HG) cervical squamous intraepithelial lesions (SIL) and in normal exocervix and transformation zone biopsies. Our results show that the average level of IL-12 increases within both the LG and HG SIL, compared with both control groups. Interestingly, the percentage of HG SIL expressing IL-12p40 was lower compared with LG SIL. In contrast, the expression of IL-10 increased in parallel with the severity of the lesion to a maximal level in HG SIL. Using immunohistochemistry, we ascertained the presence of IL-12 protein in SIL and IL-10 protein in the transformation zone and SIL biopsies. Both IL-12- and IL-10-producing cells were localized in the stroma, not within the SIL. Furthermore, in this study we also observed that the region of the cervix the most sensitive to lesion development, the transformation zone, was associated with higher average levels of the immunosuppressive cytokines IL-10 and TGF-β1.
Compartmentalized transgene expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mouse lung enhances allergic airways inflammation
Authors: Lei X-F , Ohkawara Y , Stämpfli M R , Gauldie J , Croitoru K , Jordana M , Xing Z 
Published: March 2003

SUMMARYTo investigate the role of GM-CSF in asthmatic airways inflammation, we have targeted GM-CSF transgene to the airway cells in a mouse model of ovalbumin (OVA)-induced allergic airways inflammation, a model in which there is marked induction of endogenous IL-5 and IL-4 but not GM-CSF. Following intranasal delivery of a replication-deficient adenoviral gene transfer vector (Ad), transgene expression was found localized primarily to the respiratory epithelial cells. Intranasal delivery of 0.03 × 109 plaque-forming units (PFU) of AdGM-CSF into naive BALB/c mice resulted in prolonged and compartmentalized release of GM-CSF transgene protein with a peak concentration of ≈ 80 pg/ml detected in bronchoalveolar lavage fluid (BALF) at day 7, but little in serum. These levels of local GM-CSF expression per se resulted in no eosinophilia and only a minimum of tissue inflammatory responses in the lung of naive mice, similar to those induced by the control vector. However, such GM-CSF expression in the airways of OVA-sensitized mice resulted in a much greater and sustained accumulation of various inflammatory cell types, most noticeably eosinophils, both in BALF and airway tissues for 15–21 days post-OVA aerosol challenge, at which times airways inflammation had largely resolved in control mice. While the levels of IL-5 and IL-4 in BALF and the rate of eosinophil apoptosis were found similar between different treatments, there was an increased number of proliferative leucocytes in the lung receiving GM-CSF gene transfer. Our results thus provide direct experimental evidence that GM-CSF can significantly contribute to the development of allergic airways inflammation through potentiating and prolonging inflammatory infiltration induced by cytokines such as IL-5 and IL-4.
Pigeon fanciers' lung: effects of smoking on serum and salivary antibody responses to pigeon antigens
Authors: Baldwin C I , Todd A , Bourke S , Allen A , Calvert J E 
Published: March 2003

SUMMARY
A reduced prevalence of pigeon fanciers' lung has been reported in pigeon breeders who smoke cigarettes. Serum and salivary antibodies to pigeon intestinal mucin and pigeon serum proteins were investigated in 227 pigeon fanciers, subdivided according to smoking habit and clinical status. Smokers had a lower incidence of precipitating antibodies to pigeon antigens and lower titres of serum IgG and IgA antibodies to mucin and to pigeon serum proteins in ELISA compared with non-smokers and ex-smokers. In contrast, IgG antibody titres to tetanus toxoid were similar in smoking and non-smoking groups. In contrast to serum antibodies, salivary IgA antibody titres to pigeon antigens were similar in smokers and non- or ex-smokers. Approximately one third of the smokers reported symptoms consistent with pigeon fanciers' lung but did not have precipitating antibodies. Only some individuals with precipitating antibodies had disease symptoms, and IgG antibody titres in these individuals were not significantly higher than in many asymptomatic individuals. Salivary IgA titres against pigeon mucin were significantly higher in asymptomatic individuals, consistent with a protective role for these antibodies. The results confirm that smoking is associated with a decreased serum antibody response to inhaled pigeon antigens, affecting IgG1, IgG2 and IgA responses, but this impairment does not extend to salivary IgA or to antibody responses to a parenterally administered protein antigen. The fact that responses to pigeon serum proteins and to pigeon intestinal mucin were similarly affected suggests that cigarette smoking depresses both T-independent and T-dependent responses to inhaled antigens.
Origin and properties of soluble CD21 (CR2) in human blood
Authors: Ling N R , Hardie D L , Johnson G D , Maclennan I C M 
Published: March 2003

SUMMARYBy analysis with a panel of CD21 MoAbs it is shown that a large part of the soluble CD21 in human blood plasma is of the long isoform (CD21L), as judged by comparison with antigen produced by mouse L cells transfected with CD21L-cDNA and reactivity with the restricted CD21 MoAb R4/23. This is compatible with the hypothesis that soluble CD21 in the blood is mainly derived from follicular dendritic cells (FDC). Cells from a human keratinocyte cell line transfected with cDNA from the Burkitt lymphoma cell line Raji also produced soluble CD21L (sCD21L), whereas the short form of sCD21 (sCD21S) was the major component of sCD21 produced by the B lymphoblastoid cell line LICR-LON-HMy and the T cell line Jurkat. Confocal studies of FDC isolated from human tonsil revealed that CD21 was present in the cytoplasm. On gel filtration sCD21 from untreated serum has an apparent size considerably greater than the 130 kD found by SDS–PAGE analysis. This may be partly accounted for by the non-globular shape of the molecule, but may also indicate, as reported by others, that in its native state sCD21 is complexed with other proteins. However, no evidence of complexing with sCD23 or C3d could be found.
Macrophage function in alloxan diabetic mice: expression of adhesion molecules, generation of monokines and oxygen and NO radicals
Authors: Ptak W , Klimek M , Bryniarski K , Ptak M , Majcher P 
Published: March 2003

SUMMARYThe increased incidence of bacterial and mycotic infections in poorly controlled diabetic patients or animals is frequently attributed to impaired activities of professional phagocytes (granulocytes, macrophages) in hypoinsulinaemic milieu. We measured production of monokines (IL-6 and tumour necrosis factor-alpha (TNF-α)), active NO and reactive oxygen intermediates (ROIs), as well as expression of several cell surface adhesion molecules (Mac-1, -2 and -3, intercellular adhesion molecule-1 (ICAM-1) and FcγRII), by thioglycollate medium-induced peritoneal macrophages of normoglycaemic and alloxan diabetic CBA/J mice (blood glucose level in the range 300 or 500 mg/dl). Macrophages of animals with moderate diabetes (300 mg/dl) produced significantly more IL-6 and TNF-α and ROIs than cells of control mice and showed an increased expression of all cell surface molecules, except Mac-3. NO/NO2 production was not affected. Administration of insulin restored enhanced values to normal levels, except for the production of ROIs which remained unusually high. We conclude that two separate mechanisms influence macrophage physiology in diabetes—lack of saturation of insulin receptors on macrophages and an indirect effect due to formation of advanced glycosylation endproducts (AGE) on their surfaces. The latter is possibly responsible for increased generation of ROIs, since it cannot be down-regulated by prolonged insulin treatment. How the increased activity of macrophages of moderately diabetic mice (enhanced production of proinflammatory monokines and oxygen radicals as well as expression of molecules) is related to their ability to kill bacteria is now under investigation.