bluuebunny/crossref_metadata_2025_split huggingface dataset:
Encapsulation ofCryptococcus neoformansregulates fungicidal activity and the antigen presentation process in human alveolar macrophages
Authors: VECCHIARELLI A , PIETRELLA D , DOTTORINI M , MONARI C , RETINI C , TODISCO T , BISTONI F 
Published: July 2010

SUMMARYOur previous studies have shown that unstimulated alveolar macrophages (AM) play a predominant role as antigen-presenting cells in Cryptococcus neoformans infections, while the function as effector cells seems to be of minor relevance. The present study focuses on the role of encapsulation of C. neoformans on fungicidal activity and the antigen presentation process of AM. Fungicidal activity in unstimulated AM occurs to a higher degree when the acapsular strain is employed, but this is impaired compared with other natural effectors, such as peripheral blood monocytes (PBM) and polymorphonuclear (PMN) cells. Cryptococcus-laden AM also induce a higher proliferative response in autologous CD4+ lymphocytes when the acapsular strain is used compared with encapsulated yeast. The enhanced blastogenic response is, in part, ascribed to an augmented IL-2 production by T cells. In addition, higher levels of interferon-gamma (IFN-γ). but not 1L-4, are produced by the responding T cells, when the acapsular strain is used compared with the encapsulated yeast. Moreover, IFN-γ) is able to induce fungicidal activity in AM against the encapsulated yeast and augments killing activity of the acapsular strain. This phenomenon is not mediated by nitric oxide production, but is correlated with an enhancement of fungicidal activity of cytoplasmic cationic proteases. We speculate that encapsulation of C. neoformans could down-regulate the development of the immune response mediated by Cryptocaccus-laden AM al lung level.
Specificity of antibodies induced after immunization of mice with the mycobacterial heat shock protein of 65 kD
Authors: BARRIOS C , TOUGNE C , POLLA B S , LAMBERT P-H , DEL GIUDICE G 
Published: July 2010

SUMMARYWe have previously shown in mice and monkeys that mycobacterial heat shock proteins (hsp) of 65 and 70 kD exert a strong in vivo helper effect when conjugated to synthetic peptides or bacterial oligosaccharides and given in the absence of any adjuvants. Considering the degree of homology existing in the phylogeny among hsp belonging to the same family, we studied whether antibodies induced in mice with this protocol of immunization with the mycobacterial 65-kD hsp (hsp65) would cross-react, and to what extent, with hsp homologues from other origins, notably with the Escherichia coli GroEL protein and with the human homologue (hsp60). The results obtained show that antibodies to the mycobacterial hsp65 cross-reacted with the E. coli GroEL protein, both in ELISA and Western biol experiments, but not with the human hsp60. In competitive ELISA experiments, the binding of these antibodies to solid-phase hsp65 was very effectively inhibited by low concentrations of the mycobacterial hsp65; however, for human hsp60. 100 times higher concentrations were required in order to obtain similar patterns of inhibition-Finally, murine antibodies to the mycobacterial hsp65 always failed to give positive results in Western biol experiments using extracts of murine cells. Taken together, these data suggest that, after immunization of mice with the mycobacterial hsp65 conjugated to peptides or oligosaccharides in the absence of adjuvants, anti-hsp65 antibodies are induced which cross-react well with hsp homologues from other prokaryotes (e.g. E. coli GroEL), but which weakly bind the human hsp homologue. These results may have implications for the potential use of microbial hsp molecules in the design of conjugated vaccine constructs.
Antiendothelial cell antibodies can be cytotoxic to endothelial cells without cytokine pre-stimulation and correlate with ELISA antibody measurement in Kawasaki disease
Authors: KANEKO K , SAVAGE C O S , POTTINGER B E , SHAH V , PEARSON J D , DILLON M J 
Published: July 2010

SUMMARYTo confirm the presence of antiendothelial cell antibodies (AECA) and study the clinical value of their measurement in Kawasaki disease (KD), sera from patients with KD were assessed for binding to human umbilieal vein endothelial cells (HUVEC) using a cellular based ELISA, and for complement-mediated cytotoxicity using 111 In-labelled HUVEC. In the ELISA assay, IgM AECA were detected in 16/22 sera, whereas IgG AECA were only present in one out of 19 sera. There was a significant difference in IgM AECA titres when comparing patients with controls. Eight out of 16 sera showed cytotoxicity against HUVEC, and this was significantly enhanced when HUVEC were pretreated with tumour necrosis factor (TNF). IgM AECA titres measured by ELISA were positively correlated with their cytotoxicity. The findings suggest that IgM class AECA in sera from patients with KD are detectable by ELISA method, and that some of these antibodies. 50% in this study, can mediate complement-dependent cytotoxicity against endothelial cells.
Cytokines and autoimmunity
Authors: CAVALLO M G , POZZILLI P , THORPE R 
Published: July 2010

SUMMARYAlthough the immunopathology of most autoimmune diseases has been well defined, the mechanisms responsible for the breakdown of self-tolerance and which lead to the development of systematic and organ-specific autoaggression are still unclear. Evidence has accumulated which supports a role for a disregulated production of cytokines by leucocytes and possibly other cells in the pathogenesis of some autoimmune diseases. However, due to the complexity and heterogeneity of cytokine effects in the regulation of the immune response, it is difficult to determine whether abnormalities in the patterns of cytokine production are primary or secondary to the pathological process. Confusion is also caused by the fact that the biological activities of cytokines are multiple and often overlapping, and consequently it is difficult to focus on a unique effect of any one cytokine. Characterization of the potential and actual involvement of cytokines is important not only for a better understanding of the pathogenesis of autoimmune conditions, but particularly because of the implications for the development of immunotherapeutic strategies for the prevention and treatment of the diseases.
Human anti-fibronectin antibodies in systemic lupus erythematosus: occurrence and antigenic specificity
Authors: ATTA M S , POWELL R J , HOPKINSON N D , TODD I 
Published: July 2010

SUMMARY
Sera from patients with connective tissue diseases exhibit autoantibodies to a spectrum of extracellular matrix proteins. Antibodies binding to solid phase bovine fibronectin (Fn) were investigated by ELISA in patients with systemic lupus erythematosus (SLE). Sera showing binding of 2 s.d. above the mean of the normal human control were considered positive and 43/150 SLE sera (28·7%) demonstrated such binding. These antibodies were mainly IgG and IgA as determined by isotype-specific ELISA. Specificity studies on selected positive sera revealed that binding was inhibited by preincubation with soluble Fn. but not with thyroglobulin or type 1 collagen. The binding was demonstrated not to be related to interactions with rheumatoid factor, complement components or immune complexes. Additional studies to determine which Fn fragment is bound by naturally occurring anti–Fn antibodies demonstrated that the binding was predominantly to the 30-kD collagen binding domain (CBD) of Fn molecule. Inhibition studies using 120-kD, 40-kD and 30-kD Fn fragments confirmed that this binding site was the 30-kD CBD.
Suppression of hen egg lysozyme-induced arthritis by intravenous antigen administration: no role in this for antigen-driven bystander suppression
Authors: JACOBS M J M , VAN DEN HOEK A E M , VAN DE PUTTE L B A , VAN DEN BERG W B 
Published: July 2010

SUMMARYThe induction of tolerance, particularly by intervention before established immunity, is widely accepted. We studied the effects of intravenous (i.v.) administration of hen egg lysozyme (HEL). before as well as after immunization, on a HEL-induced arthritis. Arthritis and also cartilage destruction were almost completely suppressed when 100 μg HEL was injected before immunization. Antigen-specific proliferative T cell responses and IL-2 production in vitro were inhibited. Antigen-specific immunogiobulin and IgG1 titres were equal in control and tolerized mice, in contrast to lowered IgG2a titres in tolerized animals. Detailed histological studies showed that the immune complex-dependent polymorphonuclear cell phase (&lt;24 h after arthritis induction) was equal for control and HEL-injected mice. Only in the T cell-dependent phase of the arthritis (&gt; 24 h), did suppression become pronounced in tolerized mice. I.V. administration of 100 μg HEL after immunization could only marginally reduce infiltrate and exudate. and no reduction of cartilage destruction was seen. An elegant way to interfere in an established immunity can be offered by creation of bystander suppresson. We show that i.v. administration of HEL followed by triggering with HEL, at the moment either of immunization or of arthritis induction., does not reduce a methylated bovine serum albumin (BSA)-arthritis. We conclude that arthritis can be suppressed almost totally when HEL is injected intravenously before immunization. Treatment after immunization is less effective. The i.v. induced suppression is Tcell-mediated and antigen-specific: no bystander suppression circuit can be generated.
Role of membrane-associated lymphotoxin (mLT) in the killing activity of lymphokine-activated killer (LAK) cells towards various tumour cell lines
Authors: HORIUCHI A , ABE Y , MIYAKE M , KIMURA K , HITSUMOTO Y , TAKEUCHI N , KIMURA S 
Published: July 2010

SUMMARYHuman lymphokine-activated killer (LAK) cells developed by an incubation of peripheral mononuclear cells with IL-2 express the membrane-associated lymphotoxin (LT)-related molecule (mLT). By a further cultivation of mLT expressing (mLT-positive) LAK ceils for 24 h without IL-2. mLT disappears (mLT-negative LAK cells). Cytotoxicities of various tumour cell lines by either mLT-positive or -negative LAK cells were compared. Eight out of 12 tumour cell lines, less susceptible to mLT-negative LAK cells than mLT-positive LAK cells, were categorized as group A, Two tumour ceils (K562 and Moit-4) had the same susceptibility to both kinds of LAK cells. The others (Daudi and Jurkat) had less susceptibilities only when they were assessed at E:T ratios of less than 5. The four tumour cell lines in the latter two cases, containing K562. Moit-4. Daudi and Jurkat cells, were categorized as group B. The cytotoxicities of group A tumour cells, but not group B tumourceils, by LAK cells were significantly suppressed by the presence of anti-LT antibody. Group A tumour ceils had higher LT-binding ability (2·82-16·44 fmol/106 cells) than group B tumour cells (less than 1·46 fmol/106 cells). Both mLT-positive and -negative LAK cells had similar perform activities and tumour cell-binding capacities. These results suggest that the mLT-mediated killing mechanism is involved in tumour ceil killing by LAK cells. Further, various tumour cell lines can be classified into two large groups according to their susceptibilities to the mLT-mediated killing by LAK cells.
Human T cells in hu-PBL-SCID mice proliferate in response to Daudi lymphoma and confer anti-tumour immunity
Authors: MALKOVSKA V , CIGEL F , STORER B E 
Published: July 2010

SUMMARYIn vitro culture of human peripheral blood lymphocytes (PBL) with Daudi (Burkitt lymphoma) cells results in selective proliferation of Vγ9/Vδ2 T cells with high cytotoxicity against Daudi cells. After adoptive transfer into severe combined immunodeficient (SCID) mice, these cells exert specific anti-tumour activity against Daudi lymphoma. To test whether cytotoxic Vγ9/Vδ2 T cells are induced in SCID mice, human PBL injected intraperitoneally were stimulated with irradiated Daudi cells (PBL/ Daudi-SCID). After 7–14 days, PBL/Daudi-SCID had a significantly higher percentage of human γδ T cells in their peritoneal cavity, lymph nodes and blood than controls (PBL-SCID). DNA content analysis of T cell subsets from PBL/Daudi-SCID showed a significantly higher percentage of cells in S + G2+M phases of the cell cycle in the TCR-γδ-1+ than in CD3+ cell population. Human cells recovered from PBL/Daudi-SCID showed specific cytotoxicity against Daudi cells. PBL/Daudi-SCID inoculated with a lethal dose of Daudi lymphoma survived significantly longer than controls. This protection was specific for Daudi cells and was not mediated by murine natural killer (NK) cells. Thus human peripheral blood T cells grafted in SCID mice proliferate in response to antigen and confer specific immunity.
Collectins, collectin receptors and the lectin pathway of complement activation
Authors: MALHOTRA R , LU J , HOLMSKOV U , SIM R B 
Published: July 2010

SummaryThe collectins are a group of soluble multimeric lectins, which contain collagenous segments, and resemble the complement protein Clq in aspects of their structures and functions. This group of proteins, which includes MBP, SP-A, SP-D, conglutinin and CL-43, are known to act as opsonins in various circumstances, and are likely to have roles in innate immunity. The focus of current research is to pursue the hypothesis that the collectins recognize and bind to non-host carbohydrate structures on microorganisms and particles, and participate in the processing or elimination of such material, either by direct interaction with phagocytic cell receptors, or by indirect routes such as complement activation.
Amelioration of established murine collagen-induced arthritis with anti-IL-1 treatment
Authors: VAN DEN BERG W B , JOOSTEN L A B , HELSEN M , VAN DE LOO F A J 
Published: July 2010

SUMMARYInflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis. To validate a key role for IL-1 in arthritic processes we have studied the protective effect of neutralizing antimurine IL-1 antibodies in the murine collagen-induced arthritis (CIA) model. Combination of anti-IL-1α and anti-IL-1β given before onset of arthritis was shown to prevent disease completely. Remarkably, a single treatment was also highly effective in the established phase of arthritis, reducing both inflammation as well as cartilage destruction. Suppression was most pronounced with the combination, but anti-IL-1β alone also induced significant relief. Finally, we studied the protective effect of IL-1 neutralization on cartilage metabolism in a unilateral expression model of collagen arthritis. To this end zymosan was injected in one knee joint before onset of disease, resulting in accelerated expression in that particular joint and the draining paw. Anti-IL-1 treatment started after accelerated expression of arthritis was able to fully normalize chondrocyte synthetic function, which was highly suppressed in the control group. It is concluded that IL-1 is an important determinant in both inflammation and cartilage destruction in collagen arthritis, and this may have implications for therapy in human arthritis.
Endothelial serpins—protectors of the vasculature?
Authors: FORSYTH K D , TALBOT V , BECKMAN I 
Published: July 2010

SUMMARY
Vascular damage, initiated by host inflammatory cells, is a component of the pathophysiology of many acute and chronic inflammatory disorders. Neutrophil-mediated tissue damage is mediated primarily by proteinases, particularly elastase and cathepsin G. In this study we have identified endothelial binding of two key serine proteinase inhibitors (serpins), α-antitrypsin, the inhibitor of elastase, and α1-antichymotrypsin, the inhibitor of cathepsin G. These serpins are shed from the endothelium into the supernatant when neutrophils adherent to the endothelium are activated. Endothelium activated by lipopolysaccharide (LPS) augments this process. Serpin-proteinase complexes activate neutrophils and induce further cytokine release, thereby amplifying inflammatory processes. Strategies aimed at preventing endothelial serpin depletion may help minimize vascular damage during inflammation.
High levels of anti-phospholipid antibodies in uncomplicated and severePlasmodium falciparumand inP. vivaxmalaria
Authors: FACER C A , AGIOSTRATIDOU G 
Published: July 2010

SUMMARYThe majority (75%) of adult patients with uncomplicated Plasmodium falciparum and P. vivax malaria are positive for anti-phospholipid antibodies (aPLA) as demonstrated by ELISA using a panel of anionic and cationic phospholipids. The highest IgG and IgM binding was to the anionic phospholipids, phosphatidylserine (PS). phosphatidic acid (PA) and cardiolipin (CL), but excluding phosphalidylinositol (PI) to which only low antibody levels were found. Comparison of the mean IgG and IgM aPLA showed a trend for anti-PA &gt; CL&gt; PS&gt;PC&gt; PE&gt; PI, Anti-PI levels were compared in two groups of African children, one group with non-severe and the other with severe (cerebral) falciparum malaria. Children with cerebral disease had significantly lower IgM anti-PI. The results are discussed with the view that serum-derived aPLA may have a role in “anti-disease” immune responses. Their possible role in the opsonization and phagocytosis of parasitized erythrocytes and in thrombocytopenia is also considered.
Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and function on cultured human glomerular epithelial cells
Authors: GARNER C M , RICHARDS G M , ADU D , PALL A A , TAYLOR C M , RICHARDS N T , MICHAEL J 
Published: July 2010

SUMMARYGlomerular epithelial cells are involved in extracapillary inflammation (crescents) but the mechanisms of this extracapillary accumulation of macrophages, epithelial cells and occasional lymphocytes are unknown. Human glomerular parietal epithelial cells express ICAM-1 and VCAM-1 on immunohistological stains of renal biopsies. We studied the expression of these cell adhesion molecules on cultured human glomerular epithelial cells (HGEC), their regulation by pro-inflammatory cytokines, and their role in mediating the adhesion of concanavalin A (Con A)-activated peripheral blood mononuclear cells. Human glomerular epithelial cells in culture constitutively express ICAM-1 and VCAM-1. The expression of ICAM-1 was not significantly altered by tumour necrosis factor-alpha (TNF-α) (P= 0·32), IL-β (P= 0·24), interferon-gamma (IFN-γ) (P=0·66) or IL-4 (P = 0·85). VCAM-1 expression was increased by all four cytokines, but only significantly so by IL-4 (P= 0·0001). Con A-stimulated, monocyte-depleted peripheral blood lymphocytes bound to human glomerular epithelial cells, median 28·9% (range 14·5–37·9%). This adherence was significantly inhibited by anti-ICAM-1 (P=0·03) and anti-LFA-1 (P=0·02), but not by anti-VCAM-1 (P= 0·13) or by antibody to von Willebrand factor (P= NS). The interaction between ICAM-1 on HGEC and LFA-1 on mononuclear cells may be important in the pathogenesis of extracapillary inflammation in glomerulonephritis.
Immunological effects of insulin-like growth factor-I—enhancement of immunoglobulin synthesis
Authors: ROBBINS K , MCCABE S , SCHEINER T , STRASSER J , CLARK R , JARDIEU P 
Published: July 2010

SUMMARYIn addition to its activity as a metabolic hormone and a regulator of somatic growth, insulin-like growth factor-I (IGF-I) has cytokine-like activities on lymphoid cells. A 14-day infusion of recombinant human (rh)IGF-I increased lymphocyte numbers in all the peripheral lymphoid organs examined. This increase was apparent for up to 3 weeks following cessation of hormone treatment. A second administration of rhIGF-I, given when the lymphocyte numbers in the rhIGF-I-treated mice had returned to control values, resulted in similar increases in the peripheral T and B cell populations. This increase in lymphocyte numbers had functional significance, since rhIGF-I-treated mice produced elevated antibody titres following primary of secondary antigen challenge compared with controls. In addition, when rhIGF-I-treated mice were immunized with a suboptimal dose of antigen they produced antibody titres which were equivalent lo those generated by immunization with optimal doses of antigen. When examined in vitro, addition of rhIGF-I alone to cultures of splenocytes from antigen-primed mice stimulated immunoglobulin synthesis. These studies suggest that IGF-I produced locally by thymic and bone marrow stromal cells may be a natural component of B and T cell lymphopoiesis.
Anti-centromere antibodies (ACA) in systemic sclerosis patients and their relatives: a serological and HLA study
Authors: MCHUGH N J , WHYTE J , ARTLETT C , BRIGGS D C , STEPHENS C O , OLSEN N J , GUSSEVA N G , MADDISON P J , BLACK C M , WELSH K 
Published: July 2010

SUMMARYAutoantibody reactivity to centromere proteins CENP-A, CENP-B and CENP-C was examined in 58 patients with systemic sclerosis (SSc). 218 first degree relatives and 22 spouses, HLA class II typing for HLA-DRB1 and HLA-DQA1 was performed by restriction fragment length polymorphism (RFLP) analysis in 50 families, and HLA-DRB1, HLA-DQA1 and HLA-DQB1 typing was performed by olignucleolitde typing in 44 families. Eleven probands and two relatives had ACA. The two relatives with ACA also had SSc. One relative was an identical twin sister of a pro band with ACA and the other relative was a sister of a proband with ACA. All ACA-positive probands and relatives were female, and all recognized CENP-A, CENP-B and CENP-C. The presence of at least one HLA-DQB1 allele not coding for leueine at position 26 of the first domain appeared necessary, although not sufficient for the generation of ACA, Therefore within SSc families ACA is strongly associated with female gender and disease phenotype, and is at least in part genetically determined.
Identification of antibody epitopes in the CB-11 peptide of bovine type II collagen recognized by sera from arthritis-susceptible and -resistant rhesus monkeys
Authors: TURNER S , BAKKER N P M , 't HART B A , HOLT P J L , MORGAN K 
Published: July 2010

SUMMARYSera from eight rhesus monkeys that had been immunized with native bovine type II collagen were tested for antibodies to cyanogen bromide peptides (CB peptides) of type II collagen by Western blotting. The monkeys produced IgG antibodies to a number of different CB peptides, with five out of eight animals producing antibodies to the CB-11 peptide (four arthritic, one non-arthritic). Antibody epitopes on the CB-11 peptide of bovine type II collagen recognized by these sera were investigated by epitope mapping. Peptides (8-mers overlapping by seven amino acids) representing the CB-11 region were synthesised and the sera screened for binding to these peptides to determine areas of high IgG antibody binding to this region of type II collagen. The profiles obtained were not identical, though there were some epitopes that were commonly recognized. Antibodies to one epitop, also present in human type II collagen, were found only in the sera of two animals with the severest arthritis. The technique of epitope mapping has successfully identified a number of epitopes within the CB-11 peptide of type II collagen recognized by antibodies from bovine type II collagen-immunized monkeys. Studies on the relevance of responses to the identified epitopes can now be undertaken.