bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukotriene B4-induced hyperadhesiveness of endothelial cells for neutrophils: relation to CD54
Authors: PALMBLAD J E W , LERNER R 
Published: August 2010

SUMMARYLeukotriene B4 (LTB4) induced an in vitro transient state of hyperadhesiveness in cultured human umbilical vein endothelial cells (HUVEC), leading to a 2·2-fold increase in the binding of neutrophil granulocytes (PMN), which was less than that conferred by platelet activating factor (PAF) though more than thrombin did (3·4- or 2·0-fold increases, respectively). This study concerns the role of the adhesive molecules CD 18 and CD54 for the LTB4- (as well as thrombin- and PAF-) induced endothelial hyperadhesiveness. The MoAbs 60·3 (to the CD18 molecule on PMN) and 84 H 10 (to one epitope of CD54 on the HUVEC) blocked the adherence of PMN to LTB4-treated HUVEC, whereas MoAb LB-2 (directed at another CD54 epitope) failed to do so. MoAb 84 H 10 blocked 43% of the thrombin-induccd hyperadhesiveness, whereas the PAF response was unaffected. Thus, LTB4-induced HUVEC hyperadhesiveness may therefore be related to a specific domain on the CD54 (or on an antigenically related molecule) as well as being dependent on CD 18, whereas the involvement of CD54 was much less or non-existent for the thrombin and PAF responses, respectively.
Passive immunization against tumour necrosis factor-alpha (TNF-α) and IL-lβ protects from LPS enhancing glomerular injury in nephrotoxic nephritis in rats
Authors: KARKAR A M , KOSHINO Y , CASHMAN S J , DASH A C , BONNEFOY J , MEAGER A , REES A J 
Published: August 2010

SUMMARYGlomerular injury caused by injection of heterologous anti-glomerular basement membrane antibodies (anti-GBM Ab) is increased in rats pretreated with small doses of bacterial lipopolysaccharide (LPS). We have investigated the involvement of tumour necrosis factor-alpha (TNF-α), IL-lα and IL-1 β in this phenomenon by passive immunization against these cytokines. Anti-TNF-α or anti-IL-1β antibodies given 1·5 h before the induction of nephritis significantly decreased injury in this model, whether assessed by the magnitude of albuminuria, the prevalence of glomerular capillary thrombi or the intensity of glomerular neutrophil infiltrate. Albuminuria in anti-GBM Ab alone was 11 ± 3, LPS/anti-GBM Ab 87±22, and anti-TNF-α antibodies/LPS/anti-GBM Ab 21 ±6 mg/24 h (mean ± s.e.) P&lt; 0·05. Passive immunization with antibodies to IL-1 β had a similar effect (anti-GBM Ab, 0·6±01, LPS/anti-GBM Ab, 92±19, anti-IL-1β antibodies/LPS/anti-GBM Ab 39 ± 8 mg/24 h, P&lt;0·05). The prevalence of glomerular capillary thrombi was also reduced significantly by these treatments; from 22 ± 5% to 4± 1% in the case of anti-TNF-α antibodies and 28±5% to 13±4% with anti-IL-1β antibodies. Similarly, the glomerular neutrophil infiltrate was also reduced by these treatments; from 42±3 to 25±1 in the case of anti-TNF-α and 47± 2 to 30± 1 with anti-IL-1α antibodies. In contrast, passive immunization against IL-1α had no effect on either albumin excretion (4±3, 83±22 and 77±24 mg/24 h), glomerular capillary thrombi (2±1; 19±5 and 16±3) or glomerular neutrophil infiltrate (22± 3; 47± 5 and 48± 5 from the three groups respectively). These results demonstrate that enhanced antibody mediated injury in the kidney is modulated by TNF-α and IL-14bT but not by IL-lα.
Analysis of lymphocyte phenotypes in cord blood from early gestation fetuses
Authors: PEAKMAN M , BUGGINS A G S , NICOLAIDES K H , LAYTON D M , VERGANI D 
Published: August 2010

SUMMARYUsing cord blood samples obtained from Fetuses between 16 and 40 weeks gestation, we have used a lysed whole blood flow cytometric technique to study the natural history of lymphocyte phenotypes known to be highly represented in cord blood at birth. The majority (51·0 ± 14·7%) of lymphocytes expressed CD45RA, a marker of ‘virgin’ cells and there was a correIation between increasing percentages of CD45R A+ lymphocytes and gestational age (r = 0·44, P&lt;0·01). Few cells (8·5 ± 4·2%) expressed the CD45RO marker of primed lymphocytes and very few (1·0 ± 0·7%) co-expressed CD45RA and RO, indicating little traffic between the two maturation markers. The percentage of B lymphocytes co-expressing CDS was high in the fetal circuIation (55·5±10·5%) compared with healthy adults (23·2 ± 14·3%; P&lt;0·00001) and the level of CDS+ B cells declined with gestational age in an exponential manner (r=−0·45, P&lt;0·05). Similarly, levels of T lymphocytes expressing the γδ T cell receptor (TCR) declined exponentially (r=−0·59, P&lt;0·005). These results demonstrate that lymphocytes remain almost entirely unprimed before birth. In addition, CD5+ B lymphocytes and TCR-γδ+ T lymphocytes decline exponentially towards birth, in a manner suggesting that they may be seeding peripheral sites such as the spleen, skin and mucosae.
Changes in natural immunity during the course of HIV-1 infection
Authors: BRENNER B G , GRYLLIS C , GORNITSKY M , WAINBERG M A 
Published: August 2010

SUMMARYThe role of natural killer (NK) and lymphokine-activated killer (LAK) cell-mediated cytotoxiciry in AIDS has yet to be established. The objective of this study was to determine inducible LAK cell responses at different stages of HIV-1 infection, and specifically to establish the participation of CD8 lymphocytes in these responses. Peripheral blood lymphocytes (PBL) were isolated from healthy seronegative (CDC-0) subjects and HIV-1 individuals who were clinically asymptomatic (Centre for Disease Control group 2, CDC-2) or symptomatic (CDC-4) with regard to secondary opportunistic infection (OI). LAK cells were generated upon incubation of PBL with IL-2 and their cytolysis of K562 and U-937 targets was determined using chromium release assays. The role of CD8+ lymphocytes as progenitors and effectors of these LAK cell responses was determined by immunomagnetic depletion of CD8+ cells from precursor PBL and LAK cells, respectively. LAK cell-mediated cytotoxicities in HIV-1-infected individuals were reduced compared with scronegativc controls without any corresponding changes in the relative proportions of CD56+ (NK) cells among groups. Depletions of CD8+ subsets from either PBL or LAK cells dramatically reduced total LAK cytotoxic responses and LAK activities per unit CD56+ cell in the OI-CDC-2 scropositive population. No corresponding changes in LAK activities in seronegative control or HIV+/OI+ CDC-4 groups were observed. Levels of LAK activity against K562 targets in CDC-0/HIV and CDC-4/HIV+ groups correlated with the percentage of CD56+ LAK cells; corresponding LAK activity in the CDC-2/HIV+ group correlated with the percentage of both CD56+ and CD8+ subsets. These findings suggest that adaptive changes in non-MHC restricted cytotoxic responses occur in HIV-1 individuals at early stages post-HIV infection, before the onset of opportunistic infection.
Elevated serum levels of IL-8 in patients with HIV infection
Authors: MATSUMOTO T , MIIKE T , NELSON R P , TRUDEAU W L , LOCKEY R F , YODOI J 
Published: August 2010

SUMMARYScrum levels of IL-8 were determined in HIV-infected individuals and the results were compared with those for HIV controls. The IL-8 levels were measured by an ELISA with a MoAb and a polyclonal antibody to recombinant IL-8. The means and 95% confidence intervals of IL-8 in sera of 36 HIV-infected individuals and 32 matched controls were 275 and 216 349 pg/ml, and 8 and 4 14 pg/ml, respectively, showing a 34-fold increase in IL-8 in the circulation of HIV-infected individuals. This increase does not appear to be related to the disease state, infection or systemic medical agents. This finding suggests the possible involvement of IL-8 in the pathogenesis of HIV-induced disease.
Ring-infected erythrocyte surface antigen (Pf/155RESA) induces tumour necrosis factor-alpha production
Authors: PICOT S , PEYRON F , DELORON P , BOUDIN C , CHUMPITAZI B , BARBE G , VUILLEZ J P , DONADILLE A , AMBROISE-THOMAS P 
Published: August 2010

SUMMARYCerebral malaria is probably related to an overstimulation of the immune system and the cytokinc network. We have previously demonstrated that tumour necrosis factor (TNF) secretion by human macrophages can be induced by soluble and heat-stable malarial antigens. Indirect evidence from epidemiological and in vitro studies suggests that Pf155/RESA can be considered as a candidate for triggering TNF secretion. Thus we conducted experiments to investigate the relationship between Pf155/RESA and TNF production. The SGE1 strain of Plasmodium falciparum was compared with the P. falciparum FCR3 strain, which does not express Pf155/RESA protein, for ability to induce TNF secretion by normal human macrophages in vitro. Synthetic peptides from the Pf155/RESA antigen ((EENV)4, (EENVEHDA)4, (DDEHVEEPTVA)3), were used in some experiments. TNF levels were measured by an immunoradiometric assay. We observed that the RESA-defective strain induces lower levels of TNF after schizont rupture than the SGE1 strain. Moreover, substantial TNF secretion was detected when macrophages were incubated with all three peptides, maximum levels being obtained with the(EENV)4 peptide. Although previous reports have described TNF-inducing activity of phospholipid from P. falciparum, these findings strengthen the evidence for Pf155/RESA antigens also being involved in TNF production during malaria.
Determination of soluble CD21 as a parameter of B cell activation
Authors: HUEMER H P , LARCHER C , PRODINGER W M , PETZER A L , MITTERER M , FALSER N 
Published: August 2010

SUMMARYIn this study we established a novel solid-phase immunoassay for CD21 using the time-resolved fluorescence of lanthanide chelates. The capture assay was able to detect concentrations of as low as 100 pg of CD21 antigen per millilitre of sample and was used for quantitative determination of CD21 in lysates of different cell lines as well as in patient serum specimens. CD21 was measured in lysates of tonsils and cell lines of B. T cell and myelomonocyte lineage, and appeared to consist of monomeric antigen under the detergent conditions used. Elevated levels of soluble CD21 were observed in serum of patients with Epstein Barr virus (EBV) infection, a disease known to be associated with polyclonal B cell activation, and in infection with the lymphotropic rubella virus. Significantly increased levels were also found in malignancies which are associated with EBV. In patients with nasopharyngeal carcinoma (NPC), a correlation with the titre of EBV-specific IgA was observed, thus supporting a possible role of soluble CD21 as a marker for disease activity in certain malignancies. Our data suggest that measurement of soluble CD21 could serve as a marker for activation of the immune system and diseases involving the B cell lymphoid system. Possible mechanisms and functions of soluble CD21 are discussed.
Early induction of IL-1 receptor antagonist (IL-1Ra) in infants and children undergoing surgery
Authors: NUALLÁIN E M Ó , PURI P , REEN D J 
Published: August 2010

SUMMARYThe cytokine response to injury or trauma is of interest in terms of both its mediation of the acute phase response and its possible relation to the immunological depression observed after major surgery. In this study, the production of cytokines IL-1 β, tumour necrosis factor-alpha (TNF-α), IL-6 and the naturally occurring inhibitor of IL-1, IL-1Ra, have been investigated in infants and children undergoing Swenson's pull-through operation for Hirschsprung's disease. Samples of peripheral blood were taken before, during and after surgery for the measurement of cytokines. IL-IRa levels increased significantly (P &lt;0.01) at 2 h after commencement of surgery, with maximal levels for individual patients being attained between 3 h and 5 h (range 7.6–67.9 ng/ml). The mean level of IL-1 Ra was maximal (26.2 ng/ml) at 5 h and returned to baseline levels between 24 h and 72 h. There were no changes observed in the circulating levels of IL-1β in nine out of 11 patients following commencement of surgery. TNF-α levels did not increase in any of the patients studied. IL-6 levels increased significantly (P&lt;0.02) 3 h after commencement of surgery, reaching maximum concentrations at 24 h (range 20–670 pg/ml), with levels falling between 48 h and 72 h. This study demonstrates, in vivo, the independent induction of IL-IRa without a concomitant increase of IL-lβ levels after major surgery. It also shows that IL-1Ra is the earliest cytokine produced in response to surgical stress.
Suppression of anti-erythrocyte autoantibody-producing B cells by a physiological IgG-anti-F(ab')2 antibody and escape from suppression by tumour transformation; a model relevant for the pathogenesis of autoimmune haemolytic anaemia
Authors: TERNESS P , MARX U , SANDILANDS G , ROELCKE D , WELSCHOF M , OPELZ G 
Published: August 2010

SUMMARYWe showed previously that broadly reactive IgG anti-immunoglobulin autoantibodies produced by rats during the immune response suppress the B cell response. We report here on the effect of a similar human antibody on self-reactive human B cells. IgG anti-F(ab')2 was added to cultures of anti-erythrocyte autoantibody-producing B cells derived from healthy donors. A dose-dependent suppression of the antibody response was obtained (maximum at 1.3 ng IgG/106 cells). This effect was competitively inhibited by F(ab')2γ. Autoimmune haemolytic anaemia can be caused by chronic monoclonal B cell proliferation. To reproduce this condition in vitro we immortalized B cells with Epstein-Barr virus (EBV) and raised a B cell population with anti-erythrocyte autoantibody activity. These cells were electrically fused with CB-F7 tumour cells and an IgGl cold-reactive anti-erythrocyte autoantibody-producing B cell line was established. Surprisingly, the tumour cells were not suppressed by IgG anti-F(ab')2. It is known that anti-immunoglobulins selectively suppress antigen-receptor (AgR)-occupied B cells by a Fcγ-receptor (FeyRemediated mechanism. To occupy their AgR, we preincubated the tumour cells with anti-AgR antibody. In spite of this, their susceptibility to suppression was not restored. As shown by rabbit IgG-sensitized ox erythrocyte (EA)-rosetting, this refractoriness was not due to a loss of FcγR. Our experiments delineate a mechanism of peripheral B cell suppression to autoantigens, and show a way of escape from control relevant for the pathogenesis of autoimmune haemolytic anaemia.
Induction of phospholipid-binding antibodies in mice and rabbits by immunization with human β2 glycoprotein 1 or anticardiolipin antibodies alone
Authors: PIERANGELI S S , HARRIS E N 
Published: August 2010

SUMMARYAnticardiolipin (aCL) antibodies are autoantibodies present in high concentrations in patients with the antiphospholipid syndrome (APS), a disorder of recurrent thrombosis and pregnancy loss. What induces aCL antibodies is uncertain, but a recent report suggested that immunization of mice with β2glycoprotein 1 (β2GPI)in Freund's complete adjuvant (FCA) resulted in aCL antibody production in the recipient mice. Since this observation might explain how autoantibodics might be induced by poor immunogens, such as phospholipids, we decided to explore the question further. In our first series of experiments, we found that aCL antibodies were induced in mice by β2GP1 mixed with adjuvants that did not contain lipids (Adju-Prime or aluminium hydroxide). This excluded the possibility that antibody induction occurred because β2GPl formed complexes with lipids in FCA. We also found that aCL antibodies always appeared before anti-β2GPl antibodies, excluding the possibility that aCL antibodies were directed to β2GP1 or were induced by formation of anti-idiotypic antibodies (to anti-β2GPl). In experiments, we found that immunization of mice with human IgG antibodies from patients with the APS (IgG-APS), also induced aCL antibodies. Immunization with pure bovine serum albumin (BSA) did not induce aCL antibodies. We propose that aCL antibodies arc induced by proteins with high avidity for phospholipids. These proteins may be bound to phospholipids when introduced, or may bind circulating phospholipids. so transforming phospholipid molecules into immunogens. Similar mechanisms might explain autoantibody induction to other poor immunogens.
Protection of islet cells from inflammatory cell deathin vitro
Authors: BURKART V , KOLB H 
Published: August 2010

SUMMARYIslet cells cocultured with activated macrophages are lysed within 15 h in vitro. We showed previously that nitric oxide generated by macrophages is a major mediator of islet cell death. We have now probed several pathways to interfere with the chain of events leading to islet cell death. Scavenging of extracellular oxygen radicals by superoxide dismutase and catalase did not improve islet cell survival. Scavenging of extra- and intracellular oxygen radicals by two potent substances, citiolone and dimethyl-thiourea, also did not reduce islet cell lysis, while a lipid-soluble scavenger, probucol, provided partial protection. These findings argue against a synergistic action of nitric oxide and oxygen radicals in islet cell toxicity. The inhibition of poly(ADP-ribose)polymerase by 3-aminobenzamide significantly improved islet cell survival. Selective inhibitors of cyclooxygenase, such as indomethacin or acetylsalicylic acid, did not improve islet cell survival. Full protection was seen in the presence of NDGA, an inhibitor of lipoxygenase, and partial suppression was caused by BW755c, an inhibitor of both lipoxygenase and cyclooxygenase. We conclude that inflammatory islet cell death caused by activated macrophages involves the activation of arachidonic acid metabolism and of poly(ADP-ribose)polymerase, but that scavenging of oxygen free radicals provides little protection from lysis.
Correlation of serum cytokine and acute phase reactant levels with alterations in weight and serum albumin in patients receiving immunotherapy with recombinant IL-2
Authors: Deehan D J , Heys S D , Simpson W , Herriot R , Broom J , Eremin O 
Published: August 2010

SUMMARYRecombinani IL-2 (rlL-2) has been used alone or in combination wiih other chemotherapeutic agents to enhance hosl defences against caneer. Prolonged administration of high doses, required for clinical efficacy, may precipitate serious dose-limiting loxicity. rlL-2-induccd ‘vascular leak syndrome’ leads lo hypotension, renal insufficiency, respiratory disturbances and other organ dysfunctions. Serial measurements of serunicylokincs and the acute phase protein C-rcactivc protein (CRP) were performed on nine palienls who received high-dose i.v. continuous therapy with rIL-2. The infiuence of these immunological parameters upon alleralions in patients' weight and serum albumin, as indicators of toxicity, was assessed. All patients experienced weight increases during the cycle (3-11% of total body weight). The serum levels of tumour necrosis factor (TNF-a) and CRP were highly predictive of aileralions in patients' weight (both P&lt;0·001), while no correlation was found with lL-6 and weight change. Serum albumin tell linearly throughout the infusion cycle, but this showed no correlation with variations in serum levels of IL-6, TNF-α, or CRP. The complement components C3 and C4 were significantly reduced at thccndofthc infusion, suggesting a possible role for this cascade system in mediating ihesc clinical changes. The strong association between serum TNF-α and weight change, not previously documented, further supports the hypothesis that TNF-α is a key mediator in the pathogenesis of the ‘vascular leak syndrome’.
Photodynamic therapy; a comparison with other immunomodulatory treatments of adjuvant-enhanced arthritis in MRL-lpr mice
Authors: RATKAY L G , CHOWDHARY R K , NEYNDORFF H C , TONZETICH J , WATERFIELD J D , LEVY J G 
Published: August 2010

SUMMARYAlthough numerous experimentat immunomodulalory regimens have been reported to be effective in the treatment of rheumatoid arthritis, they also produce undesirable side effects. An alternative specific modality of localized treatment is photodynamic therapy (PDT). In this study we treated 13-week-old MRL-lpr mice whose spontaneous arthritis was enhanced by intradermal injection of Freund's complete adjuvant (FCA). One group received transcutaneous photodynamic therapy at days 0, 10, and 20, following the FCA injection. The other groups were injected with 1 mg/kg per day indomethacin, 40 mg/kg per day cyclosporin A (CsA), or treated with 3 Gy sublethal whole body irradiation (WBI). The development of swelling was monitored for 1 month, at which time proteinurca, lymphadenopathy and the histopathology of the joints and kidneys were assessed. The results demonstrated that PDT and the conventional treatments significantly ameliorated swelling of the hindlimbs from 70%in the untreated FCA-injected animals to below the 19% level characteristic of the unmanipulated control. Histological examination showed a reduction in pannus fornamtion, and cartilage and bone destruetion, the characteristics of adjuvant-enhanced arthritis. PDT did not affect the survival rate, lymphoproliferation, or proteinuria of the treated animals. However, indomethacin increased proteinurea, and was less effective in preventing cartilage and bone destruction, furhtermore, lower doses of CsA and WBI exacerbated arthritis activity. These results indicate that photodynamic therapy can inhibit the development of adjuvant-enhanced arthritis in MRL-lpr mice with similar effectiveness to the conventional treatments, but without their negative side effects.
Epitope mapping of the 52-kD Ro/SSA autoantigen
Authors: FRANK M B , ITOH K , McCUBBIN V 
Published: August 2010

SUMMARYAutoantibodies to Ro/SSA are commonly found in sera of patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome. The presence of these antibodies is related to lymphopenia, photosensitive dermatitis, and pulmonary and renal disease, suggesting that they have an immunopathologic role [1-6]. We previously isolated a cDNA clone which encodes the 52-kD human Ro/SSA protein. In this study we have determined the number and location of epitopes recognized by SLF sera using recombinant proteins encoded by the full-length or overlapping subclones of this cDNA. An immunodominant epitope was detected using Western blots and ELISA on the NH:-terminal side of this protein's putative leucine zipper. The data suggest that 11 amino acid.s are critical for the recognition of this molecule by these autoantibodies. Although the titres of anti-52-kD Ro/SSA antibodies vary between different patient sera, no heterogeneity in the location of antigenic epitopes to which their autoantibodies bound was detected. This homogeneous pattern of reactivity to a single rather than multiple regions of this protein is unusual for lupus autoantigens which have been identified, and suggests that these antibodies may have arisen as by a cross-reaction to an epitope on another molecule.