bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement regulation in innate immunity and the acute-phase response: inhibition of mannan-binding lectin-initiated complement cytolysis by C-reactive protein (CRP)
Authors: Suankratay C , Mold C , Zhang Y , Potempa L A , Lint T F , Gewurz H 
Published: March 2003

SUMMARYMannan-binding lectin (MBL) is an acute-phase protein which activates complement at the level of C4 and C2. We recently reported that the alternative pathway also is required for haemolysis via this ‘lectin pathway’ in human serum. CRP is another acute-phase reactant which activates the classical pathway, but CRP also inhibits the alternative pathway on surfaces to which it binds. Since serum levels of both proteins generally increase with inflammation and tissue necrosis, it was of interest to determine the effect of CRP on cytolysis via the lectin pathway. We report here that although CRP increases binding of C4 to MBL-sensitized erythrocytes, which in turn enhances lectin pathway haemolysis, it inhibits MBL-initiated cytolysis by its ability to inhibit the alternative pathway. This inhibition is characterized by increased binding of complement control protein H and decreased binding of C3 and C5 to the indicator cells, which in turn is attributable to the presence of CRP. Immunodepletion of H leads to greatly enhanced cytolysis via the lectin pathway, and this cytolysis is no longer inhibited by CRP. These results indicate that CRP regulates MBL-initiated cytolysis on surfaces to which both proteins bind by modulating alternative pathway recruitment through H, pointing to CRP as a complement regulatory protein, and suggesting a co-ordinated role for these proteins in complement activation in innate immunity and the acute-phase response.
A variety of cytokines and immunologically relevant surface molecules are expressed by normal human skeletal muscle cells under proinflammatory stimuli
Authors: Nagaraju K , Raben N , Merritt G , Loeffler L , Kirk K , Plotz P 
Published: March 2003

SUMMARYMuscle is an attractive target for gene therapy and for immunization with DNA vaccines and is also the target of immunological injury in myositis. It is important therefore to understand the immunologic capabilities of muscle cells themselves. In this study, we show that proinflammatory stimuli induce the expression of other cytokines such as IL-6, transforming growth factor-beta (TGF-β), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by muscle cells themselves, as well as the up-regulation of human leucocyte antigen (HLA) class I, class II and intercellular adhesion molecule-1 (ICAM-1). Thus, muscle cells have an inherent ability to express and respond to a variety of cytokines and chemokines. The levels of HLA class I, class II and ICAM-1 in inflamed muscle may be affected by the secreted products of the stimulation.
Immunocytochemical localization of inducible nitric oxide synthase and transforming growth factor-beta (TGF-β) in leprosy lesions
Authors: Khanolkar-Young S , Snowdon D , Lockwood D N J 
Published: March 2003

SUMMARYInducible nitric oxide synthase (iNOS) and TGF-β were localized by immunocytochemistry in skin lesions from patients across the leprosy spectrum, and from patients undergoing reversal reaction. iNOS expression was highest at the tuberculoid pole of the spectrum, and increased during reversal reaction. TGF-β was observed throughout the leprosy spectrum, but was highest at the lepromatous pole. Levels of TGF-β decreased during reversal reaction. Reduced levels of TGF-β may contribute to unregulated inflammatory responses during reactional episodes.
Apoptosis in labial salivary glands from Sjögren's syndrome (SS) patients: comparison with human T lymphotropic virus-I (HTLV-I)-seronegative and -seropositive SS patients
Authors: Nakamura H , Koji T , Tominaga M , Kawakami A , Migita K , Kawabe Y , Nakamura T , Shirabe S , Eguchi K 
Published: March 2003

SUMMARYApoptosis is a type of cell death that occurs during morphogenesis and development of the immune system. One of the mechanisms is mediated through the Fas and Fas ligand (FasL) pathway. To determine the possible involvement of Fas and its ligand in salivary gland destruction, we analysed the appearance of nuclei with DNA fragmentation by using nick end labelling (TUNEL) and the expression of Fas and FasL by immunohistochemistry in labial salivary glands. Furthermore, we compared the features of apoptosis in labial salivary glands between HTLV-I− and HTLV-I+ SS. When the frozen sections of 10 primary SS patients in the absence of anti-HTLV-I antibody were examined, several apoptotic cells were found in the acinar and ductal epithelial cells as well as infiltrated mononuclear cells. Both Fas and FasL were detected in the infiltrated mononuclear cells. Acinar epithelial cells, which are surrounded by FasL+ mononuclear cells, were also double-positive with Fas and FasL, although the expression of FasL was localized at their apical border, suggesting that apoptosis of mononuclear cells was achieved by activation-induced mechanisms through Fas/FasL pathways, and that of acinar epithelial cells was mediated by FasL derived from either acinar epithelial cells themselves or infiltrated mononuclear cells. Interestingly, Fas expression in ductal epithelial cells was localized around the lumen side of the ducts, indicating that FasL secreted from acinar epithelial cells may induce Fas-mediated apoptosis of ductal epithelial cells. We also studied the labial salivary glands from nine SS patients with anti-HTLV-I antibodies. There was no significant difference in the occurrence of apoptotic cells or in the expression of Fas and FasL between HTLV-I+ and HTLV-I− SS patients. It was of note that neither the expression of Fas and FasL nor the presence of apoptotic cells were determined in labial salivary glands from subjects without SS. These findings indicate that Fas-mediated apoptosis in salivary glands could be involved in the pathological manifestations of SS, irrespective of HTLV-I seropositivity.
Increased nitric oxide (NO) production by antigen-presenting dendritic cells is responsible for low allogeneic mixed leucocyte reaction (MLR) in primary biliary cirrhosis (PBC)
Authors: Yamamoto K , MD Fazle Akbar S K , Masumoto T , Onji M 
Published: March 2003

SUMMARYThe levels of blastogenesis in allogeneic MLR containing T cells from one normal volunteer and irradiated dendritic cells from 29 patients with PBC, 17 patients with chronic hepatitis type C (CH-C) and 22 allogeneic normal controls were compared to see if there is any role of antigen-presenting cells (APC) in the pathogenesis of PBC. The stimulatory capacity of dendritic cells from PBC was significantly lower compared with that of dendritic cells from CH-C (P&lt; 0·05) and normal controls (P &lt; 0·05), which could not be attributable either to the levels of expression of surface molecules, such as HLA-DR and CD86 on dendritic cells, or to the levels of cytokines, such as IL-10 and IL-12. Significantly higher levels of NO were seen in the allogeneic MLR supernatants containing dendritic cells from PBC compared with the supernatants from cultures containing dendritic cells from CH-C (P &lt; 0·001) or normal controls (P &lt; 0·001). Moreover, dendritic cells from PBC produced 10 times more NO compared with dendritic cells from CH-C and normal controls (21·9 ± 2·8 μmversus 1·6 ± 0·3 μm and 1·6 ± 0·3 μm, respectively; P &lt; 0·001). The addition of NG-monomethyl-l-arginine monoacetate (L-NMMA), a known inhibitor of NO in allogeneic MLR containing dendritic cells from PBC, resulted in a significant decrease of NO and increase of blastogenesis. The selective impairment of dendritic cell function, increased production of NO by dendritic cells and restoration of blastogenesis using NO inhibitor in PBC have suggested a role for NO and dysfunction of dendritic cells in the pathogenesis of PBC. This inspires optimism that modulating the function of dendritic cells and controlling NO production, an improved therapeutic approach, might be planned for PBC.
Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-α) production acting on leucocytes resembling immature dendritic cells
Authors: VALLIN H , BLOMBERG S , ALM G V , CEDERBLAD B , RÖNNBLOM L 
Published: March 2003

SUMMARYPatients with active SLE often have an ongoing production of IFN-α. We therefore searched for an endogenous IFN-α-inducing factor (IIF) in SLE patients and found that their sera frequently induced production of IFN-α in cultures of peripheral blood mononuclear cells (PBMC) from healthy blood donors, especially when the PBMC were costimulated with the cytokines IFN-α2b and granulocyte-macrophage colony-stimulating factor (GM-CSF). The phenotype of the IFN-α-producing cells (IPC) as determined by flow cytometry corresponded to that of the natural IPC, resembling immature dendritic cells. The IIF activity in SLE sera was sometimes as high as that of a virus and was present especially in patients with active disease and with measurable IFN-α levels in serum. The IIF had an apparent molecular weight of 300–1000 kD and appeared to consist of both immunoglobulin and DNA, possibly being immune complexes. This endogenous IFN-α inducer may be of pathogenic significance, since a reported occasional adverse effect of IFN-α therapy in patients with non-autoimmune disorders is development of anti-dsDNA antibodies and SLE.
Human milk 90K (Mac-2 BP): possible protective effects against acute respiratory infections
Authors: FORNARINI B , IACOBELLI S , TINARI N , NATOLI C , DE MARTINO M , SABATINO G 
Published: March 2003

SUMMARYEighty-six children fed human milk were followed prospectively from birth to 12 months of age to assess the effect of milk 90K, a secreted glycoprotein with immune-stimulatory properties, on development of acute respiratory infections (ARI). The level of human milk 90K was inversely related to episodes of ARI (r = − 0.34; P = 0.001). The average 90K level in human milk fed to children who did not develop ARI was significantly higher than in milk fed to children in whom infection occurred on multiple occasions (156.6 ± 144.8 μg/ml versus 70.9 ± 92.3 μg/ml; P = 0.001). These data suggest that the protective effects of human milk against ARI may be due in part to immune maturation effects by secreted 90K.
IgG subclass reactivity to human cardiac myosin in cardiomyopathy patients is indicative of a Th1-like autoimmune disease
Authors: SKYLLOURIOTIS P , SKYLLOURIOTIS-LAZAROU M , NATTER S , STEINER R , SPITZAUER S , KAPIOTIS S , VALENT P , HIRSCHL A M , GUBER S E , LAUFER G , WOLLENEK G , WOLNER E , WIMMER M , VALENTA R 
Published: March 2003

SUMMARYStudies performed in mice together with the demonstration of increased levels of heart-specific autoantibodies, cytokines and cytokine receptors in sera from cardiomyopathy (CMP) patients argued for a pathogenic role of autoimmune mechanisms in CMP. This study was designed to analyse the presence of IgG anti-heart antibodies in sera from patients suffering from hypertrophic and dilatative forms of CMP as well as from patients with ischaemic heart disease and healthy individuals. Patients' sera were analysed for IgG reactivity to Western-blotted extracts prepared from human epithelial and endothelial cells, heart and skeletal muscle specimens as well as from Streptococcus pyogenes. The IgG subclass (IgG1–4) reactivity to purified human cardiac myosin was analysed by ELISA. While sera from CMP patients and healthy individuals displayed comparable IgG reactivity to a variety of human proteins, cardiac myosin represented the prominent antigen detected strongly and preferentially by sera from CMP patients. Pronounced IgG anti-cardiac myosin reactivity was frequently found in sera from patients with dilatative CMP and reduced ventricular function. ELISA analyses revealed a prominent IgG2/IgG3 anti-cardiac myosin reactivity in CMP sera, indicating a preferential Th1-like immune response. Elevated anti-cytomegalovirus, anti-enterovirus IgG titres as well as IgG reactivity to nitrocellulose-blotted S. pyogenes proteins were also frequently observed in the group of CMP patients. If further work can support the hypothesis that autoreactivity to cardiac myosin represents a pathogenic factor in CMP, specific immunomodulation of this Th1- towards a Th2-like immune response may represent a promising therapeutic strategy for CMP.
Inhibitory effects of transforming growth factor-beta (TGF-β) on certain functions of intraepithelial lymphocytes
Authors: EBERT E C 
Published: March 2003

SUMMARYHuman intraepithelial lymphocytes (IEL), CD8+ lymphocytes located between epithelial cells, are likely to be influenced by the immunosuppressive cytokine, TGF-β, secreted by epithelial cells. This study evaluates the effects of TGF-β on IEL functions. IEL were derived from proximal jejunum of patients undergoing gastric bypass operations for morbid obesity. Proliferation was determined by 3H-thymidine incorporation; IL-2 production, by ELISA; expression of IL-2 receptor, CD2, HML1, CD16, and CD56, by immunofluorescence; binding, by adherence of radiolabelled cells; and cytotoxicity by 51Cr-release assay. TGF-β (≥ 1 ng/ml) inhibited the mitosis of IEL to mitogens, IL-7, and stimuli of the CD2 and CD3 pathways. The blocking effect did not target the activation events of IL-2 production and receptor generation. Rather, it reduced cell division after activation when added 24 h after initiating the culture. Antibody neutralization of naturally occurring TGF-β increased IEL proliferation to IL-2, but not to the other stimuli. Of the multiple surface markers tested, only CD2 and HML1 expression increased with TGF-β and decreased with antibody to TGF-β, although the cytokine and the neutralizing antibody had no effects on IEL binding to colon cancer. TGF-β reduced the number of CD56+ IEL and the lymphokine-activated killing when co-cultured with IL-7 but not with IL-2 or IL-15. TGF-β inhibits certain IEL functions: the reduction in cell division rather than activation and a decline in IL-7-mediated lysis of colon cancer due to a lowering of the number of natural killer cells.
Inhibitory effects of anti-rheumatic drugs on vascular endothelial growth factor in cultured rheumatoid synovial cells
Authors: NAGASHIMA M , YOSHINO S , AONO H , TAKAI M , SASANO M 
Published: March 2003

SUMMARY
Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and is constitutively expressed in the synovium of rheumatoid arthritis (RA). Over-expression of VEGF may play an important role in pathogenic vascularization and synovial hyperplasia of RA. In the present study, we examined whether disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX) and salazosulfapiridine (SASP), act by inhibiting the production of VEGF by cultured synovial cells of patients with RA. Treatment of cultured synoviocytes with lipopolysaccharide (LPS) significantly increased VEGF production by cultured synovial cells. BUC significantly inhibited LPS-induced VEGF production, while GST tended to inhibit the production of VEGF. The inhibitory effects on VEGF production were dose-dependent. In contrast, MTX and SASP did not affect VEGF production. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that BUC also inhibited LPS-induced VEGF mRNA expression in RA synovial cells. The present study provides the first evidence that BUC inhibits VEGF production and the expression of its mRNA in synovial cells of RA patients. Our results indicate that the anti-rheumatic effects of BUC are mediated by suppression of angiogenesis and synovial proliferation in the RA synovium through the inhibition of VEGF production by synovial cells.
Leishmania-specific T cells expressing interferon-gamma (IFN-γ) and IL-10 upon activation are expanded in individuals cured of visceral leishmaniasis
Authors: KEMP K , KEMP M , KHARAZMI A , ISMAIL A , KURTZHALS J A L , HVIID L , THEANDER T G 
Published: March 2003

AbstractPeripheral blood mononuclear cells (PBMC) from patients who have recovered from visceral leishmaniasis often respond to Leishmania antigens in vitro by production of both IL-4, IFN-γ and IL-10. In order to establish the cellular sources of these cytokines, we activated cells from individuals with a history of visceral leishmaniasis with Leishmania antigen for 6 days in culture, and identified cytokine production at the single-cell level by flow cytometry. The cytokines were only found in CD3+ cells and among these mainly within the CD4+ subset. The percentage of cytokine-producing cells was compared in Leishmania-activated PBMC cultures from the previous patients and from individuals living in a village where leishmaniasis does not occur. The percentage of IL-10- and IFN-γ-containing cells was significantly higher in the previous patients than in the controls, indicating that Leishmania-specific T cells producing IL-10 and/or IFN-γ had been expanded as a result of the infection. The cytokine-producing cells in the previous patients could be divided into three types: (i) cells producing IFN-γ only; (ii) cells producing IL-4 only; and (iii) cells producing IFN-γ and IL-10 simultaneously. The first and second group of cells can be described as Th1- and Th2-type cells, respectively. The third group could be a regulatory subset of T cells important for maintaining a balance between Th1- and Th2-type cells in these individuals.
Regulation of the expression of Fcγ receptor on circulating neutrophils and monocytes in Kawasaki disease
Authors: Nakatani K , Takeshita S , Tsujimoto H , Kawamura Y , Kawase H , Sekine I 
Published: March 2003

SUMMARYTo investigate the regulation of Fcγ receptor (FcγR) expression on circulating phagocytes in Kawasaki disease (KD), we analysed the expressions of FcγRI, II and III on neutrophils and monocytes in 20 patients with KD, 10 with a bacterial infection (BI), 10 with a viral infection (VI), and 10 healthy controls (HC) using flow cytometric analysis. The KD patients had a significantly higher level of FcγRI expression on neutrophils, but not on monocytes, than the BI, VI and HC patients. FcγRII expression on neutrophils was significantly higher in KD, BI and VI than HC, but there was no significant difference in FcγRII expression among KD, BI and VI. FcγRIII expression on neutrophils in KD was significantly lower than in VI and HC, but was higher on monocytes. A kinetic analysis of FcγR expression in KD demonstrated the expression of FcγRI and II on neutrophils to decline, but no remarkable change was observed in the monocytes, from the subacute phase through the convalescent phase. In addition, FcγRIII expression on neutrophils increased, while FcγRIII expression on monocytes decreased during the time course of KD. FcγR expression in the acute phase of KD is thus characterized by markedly increased expression of FcγRI on neutrophils, followed by a subsequent decrease, and decreased expression of FcγRIII on neutrophils and increased expression of FcγRIII on monocytes followed by a reverse kinetics during the clinical course. These findings are thus considered to reflect the functional up-regulation of neutrophils and monocytes in KD.
The T cell receptor repertoire of CD8+CD28− T lymphocytes is dominated by expanded clones that persist over time
Authors: Mugnaini E N , Egeland T , Spurkland A , Brinchmann J E 
Published: March 2003

SUMMARYThe costimulatory molecule CD28 is expressed on almost all CD4+ T cells, but on only a portion of CD8+ T cells in healthy human adults. αβ T cells may thus be divided into three phenotypically and functionally different subsets: CD4+, CD8+CD28+ and CD8+CD28−. Using peripheral blood lymphocytes from six healthy adults, we have studied the T cell receptor (TCR) repertoire within these subsets by analysis of the distribution of lengths of the complementarity determining region 3 (CDR3) of the beta variable (BV) transcripts and flow cytometric analysis of TCR Vβ usage. Expanded CDR3 lengths were identified in 86% of BV families within CD8+CD28− T cells, but in only 4% within CD4+ T cells, and 35% within CD8+CD28+ T cells (P &lt; 0.01). When sequenced, the majority of expanded peaks were found to be dominated by single clones. Identical expanded clones were found within both CD8+CD28+ and CD8+CD28− subsets, consistent with the belief that CD8+CD28− T cells descend directly from CD8+CD28+ T cells. Greatly expanded CD28− clones were found within both CD8+ and CD4+ subsets and persisted at the same magnitude for up to 4.5 years of observation. The finding of a small proportion of cells expressing Ki-67 showed that some of these clonally expanded cells were in the active stages of the cell cycle, but few of the cells expressed activation markers CD69, CD25, CD71 or CD122. One likely explanation for the persistence of expanded peripheral lymphocyte populations in healthy individuals is the presence of persistent antigen.
The influence of age and gender on serum dehydroepiandrosterone sulphate (DHEA-S), IL-6, IL-6 soluble receptor (IL-6 sR) and transforming growth factor beta 1 (TGF-β1) levels in normal healthy blood donors
Authors: Young D G , Skibinski G , Mason J I , James K 
Published: March 2003

SUMMARYDysregulation of IL-6 synthesis is thought to play a role in the development of a number of age-related conditions, such as rheumatoid arthritis, osteoporosis, atherosclerosis, Alzheimer's disease and B cell malignancies. Recently it has been suggested that the production of IL-6 is influenced by the adrenal hormone dehydroepiandrosterone (DHEA) and its sulphated derivative DHEA-S. In humans we investigated the relationship between DHEA-S, IL-6, IL-6 sR and TGF-β1 in the serum of normal healthy male and female blood donors. Using immunoassay techniques we found that the serum levels of DHEA-S significantly (P = 0.0001) decreased with age in both males and females. Furthermore, mean DHEA-S levels in all age groups were significantly (P = 0.0001) higher in males. Such correlations were not apparent for IL-6 using a standard assay, but a high sensitivity assay revealed that serum IL-6 was significantly (P = 0.0018) positively correlated with age in males only. In addition, serum levels of DHEA-S were significantly (P = 0.048) negatively correlated with serum IL-6, again in male subjects only. In contrast, serum IL-6 sR and TGF-β1 levels were not correlated with age in either males or females and were not significantly different between the sexes. However, a significant (P = 0.024) negative correlation between DHEA-S and IL-6 sR was found in males. These studies clearly highlight the complex nature of the relationship between these molecules in the ageing process in normal healthy blood donors and demonstrate the need to use high sensitivity assays when measuring IL-6 in apparently healthy individuals under the age of 70 years.