bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erythrocytes from young but not elderly donors can bind and degrade immune complex- and antibody-bound C3in vitro
Authors: SHAPIRO S , KOHN D , MILLER B , GERSHON H 
Published: July 2010

SUMMARYIn situ aged erythrocytes (senescent erythrocytes from young donors and both young and old erythrocytes from elderly donors) demonstrate high levels of membrane-bound C3c and C3d and elevated susceptibility to in vitro phagocytosis. In this study we demonstrate that in situ aged erythrocytes are defective in their ability to degrade C3 fragments and clear them from the erythrocyte membrane. Erythrocytes from young donors bind complement-bearing immune complexes via CRI and become susceptible to complement-mediated erythrophagocytosis (“innocent bystander” sequestration). Erythrocytes from elderly donors are defective in their ability to bind such immune complexes, as attested by the lack of an increment in membrane-associated C3 fragments as detected by flow cytometry and lack of an increment in in vitro sequestration. Factor I (serum)-dependent cleavage of C3 fragments and release of immune complexes from the erythrocytes of young donors lead to a drop in erythrocyte-associated C3 fragments and the disappearance of the “innocent bystander” phenomenon. Inhibition of Factor I, and thus inhibition of C3b degradation and immune complex release for the erythrocyte membrane, enhances the levels of ‘innocent bystander’ sequestration of erythrocytes from young donors. Erythrocytes from elderly donors are defective in the dynamic process of CRI binding of complement-bearing immune complexes and Factor I-associated release of membrane-associated C3 fragments, A defect in the ability of all in situ aged erythrocytes to clear their membranes of C3 fragments is also demonstrated for complement bound to the erythrocyte via IgM isoagglutinins. While erythrocytes from both young and elderly donors allow for the IgM-mediated binding of complement to the erythrocyte, only young erythrocytes from young donors demonstrate degradative activity with the release of membrane-associated C3c. Erythrocytes from elderly donors demonstrate lower levels of detectable CRI (CD35). decay accelerating factor (OAF) (CD55) and Protectin (CD59) than do erythrocytes from young donors. Time course studies determine that the defect in handling of immune complexes observed for in situ aged erythrocytes is not due to differences in the kinetics of loading or releasing of immune complexes. These findings on the refractiveness of erythrocytes of elderly donors to uptake of immune complexes and the degradation of C3 fragments may be of importance not only in the understanding of erythrocyte sequestration, but also in the physiology of immune clearance in the elderly.
Some patients with anti-myeloperoxidase autoantibodies have a C-ANCA pattern
Authors: SEGELMARK M , BASLUND B , WIESLANDER J 
Published: July 2010

SUMMARY
Rapidly progressive glomerulonephritis with or without other signs of systemic vasculitis is often accompanied by antibodies to myeloperoxidase. Such antibodies normally produce a perinuclear pattern on ethanol-fixed neutrophils (perinuclear anti-neutrophil cytoplasm antibodies (PANCA)) at indirect immunofluorescence. We report here sera front three patients that are antimyeloperoxidase-positive in ELISA that instead produce a cytoplasmic pattern (classical anti-neutrophil cytoplasmic antibodies (C-ANCA)), a pattern normally seen in conjunction with antibodies to proteinase 3. These sera did not react with proteinase 3. For two of the sera the specificity of the anti-myeloperoxidase reaction was confirmed with inhibition-ELISA experiments and with immunoblotting. A mouse anti-myeloperoxidase MoAb that produces a cytoplasmic pattern is also described. Competition ELISA experiments show that this antibody and anti-myeloperoxidase sera with cytoplasmic pattern recognize epitopes that are separate from epitopes recognized by another perinuclear pattern producing anti-myeloperoxidase MoAb. Cytoplasmic pattern epitopes as well as ‘perinuclear pattern’ epitopes can be found on all three major myeloperoxidase isoforms. after separation by ion exchange chromatography. Affinity chromatography. using the eytoplasmic pattern producing anti-myeloperoxidase monoclonal antibody, shows that the epitope recognized by this MoAb is present on all myeloperoxidase molecules. This epitope is not confined to any special subpopulation. These findings indicate that all myeloperoxidase do not relocate after ethanol fixation, and that C-ANCA and P-ANCA epitopes exist simultaneously on the same myeloperoxidase molecule. We propose that the two immunofluorescence patterns arise due to different availabilities of the epitopes in the microenvironment where myeloperoxidase Is present.
IgE elevation and IgE anti-malarial antibodies inPlasmodium falciparummalaria; association of high IgE levels with cerebral malaria
Authors: PERLMANN H , HELMBY H , HAGSTEDT M , CARLSON J , LARSSON P H , TROYE-BLOMBERG M , PERLMANN P 
Published: July 2010

SUMMARYIn the course of studying immunoregulation in human Plasmodium falciparum malaria we have investigated IgE levels and IgE anti-plasmodial antibodies in children and adults from areas of high malaria endemicity in both Africa and Asia. On average, 85% of all donors had significantly elevated levels of total IgE. A fraction of the IgE had anti-plasmodial activity as revealed by ELISA with lysates of infected erythrocytes as antigen. Using synthetic peptides representing antigenic regions of two major plasmodial blood stage antigens, IgE antibody concentrations ranged from 5 to 15 ng/ml serum for each of the peptides. On average, the concentrations of the corresponding IgG antibodies were x500-I000 higher. Immunoblotting of parasite lysates showed that most donors had IgE antibodies against one or several of a restricted number of plasmodial polypeptides, with antibodies against an antigen of mol. wt 45 kD already being present in all donors at an early age. Donors having IgE antibodies to particular antigens also frequently had corresponding IgG4 antibodies, reflecting underlying IL-4-dependent cellular mechanisms controlling formation of these isotypes. As infection with other parasites such as helminths is known lo induce IgE elevation, the results do not prove that plasmodial infections were the primary cause of IgE induction. However, the importance of plasmodial infection for IgE elevation was supported by the finding of significantly higher levels of IgE., but not of IgG, in children with cerebral malaria compared with patients with uncomplicated disease.
Cytokine mRNA expression in endomyocardial biopsies during acute rejection from human heart transplants
Authors: BAAN C C , VAN EMMERIK N E M , BALK A H M M , QUINT W G V , MOCHTAR B , JUTTE N H P M , NIESTERS H G M , WEIMAR W 
Published: July 2010

SUMMARYThe immune response to an allograft is regulated by cytokines produced by cells infiltrating the allograft. However, the immunopathogenesis of allograft rejection is not completely understood. To investigate the role of cytokines after clinical heart transplantation, we analysed the expression of cytokine genes in sequentially taken endomyocardial biopsies (EMB) by using the reverse transcriptase-polymerase chain reaction (RT-PCR). We analysed 44 EMB from II recipients: 21 EMB before or during rejection, and 23 EMB without histological evidence of acute rejection. A strong correlation was found between IL-2 gene expression and histologically proved rejection (16/21 versus 1/23 without rejection, P &lt; 0·001; x2 test). Also, expression of IL-4 and IL-6 genes was more often found in EMB during rejection than in EMB without signs of rejection (IL-4, 62% versus 35%; and IL-6, 81% versus 39%. respectively). No relation with rejection or with immunological quiescence was observed for the presence of IL-10 gene transcripts. IL-10, but also IL-6 mRNA were detectable in donor heart tissue before transplantation (9/10), In contrast, IL-2 and IL-4 gene transcripts were absent in these samples. These differences could not be explained by the presence or absence of T ceils, since the gene for the constant region of the β-chain (CG) of the T cell receptor (TCR) not only was expressed in post-transplant EMB but also in pre-transplant donor heart tissue. Our results provide strong evidence that the immunoregulatory cytokines IL-2, IL-4 and IL-6 are important local regulators in the graft during acute rejection. The role of IL-10 in the immunologic response lo the transplanted organ needs further investigation.
Enhanced activation of human T cell clones specific for virus-like particles expressing the HIV V3 loop in the presence of HIV V3 loop-specific polyclonal antibodies
Authors: PEIFANG S , PIRA G L , FENOGLIO D , HARRIS S , COSTA M G , VENTURINO V , DESSI V , LAYTON G , LAMAN J , HUISMAN J G , MANCA F 
Published: July 2010

SUMMARYRecombinant virus-like particles (VLP), formed by the yeast Ty p1 protein, carrying the HIV gp120 V3 loop on their surface (V3-VLP) have been tested in vitro for immunogenicity and antigenicity by using VLP pl-specific human CD4+ T cell lines and clones. VLP-specific human T cell lines and clones were generated from normal individuals, indicating that VLP-specific precursor cells present in the peripheral lymphocyte pool can be induced to expand clonally upon antigen challenge in vitro, in the absence of previous immunization. It was also shown that V3-specific polyclonal antibodies enhance V3-VLP-induced activation of VLP-specific T cell clones. Antibody-dependent potentiation has been shown previously in other antigen systems, and it depends on enhanced uptake of complexed antigen by Fe receptor-positive antigen-presenting ceils. Since in this case antigen is internalized by presenting cells as a complex, it can be inferred that a similar event of antibody-mediated antigen uptake can take place with V3-speeific B cells, resulting in presentation by the B cells of T helper epitopes derived from processing of the VLP pi moiety. This suggests that T helper cells specific for the carrier VLP pi protein can be activated to provide help to V3-specific B ceils in the presence of the appropriate antigen construct.
Cross-reactivity studies and differential serodiagnosis of human infections caused by Trypanosoma cruzi and Leishmania spp; use of immunoblotting and ELISA with a purified antigen (Ag163B6)
Authors: MALCHIODI E L , CHIARAMONTE M G , TARANTO N J , ZWIRNER N W , MARGNI R A 
Published: July 2010

SUMMARY
Results of our studies on the reactivity of chagasic and leishmaniasic sera with the purified T. cruzi- specific antigen 163B6, as assessed by ELISA, and with complex antigenic mixtures from T. cruzi and Leishmania mexicana, by immunoblotting. are presented here. Our objective was to identify the antigens responsible for the exhibited cross-reactivity between trypanosomiasis and leishmaniasis, and to find a specific reactivity pattern corresponding to each parasitosis. In spite of the high cross-reactivity observed with the immunoblotting, the use of 7.5% A-B gels made it possible to identify a characteristic pattern for each parasitosis, that could be distinguished by the naked eye. The characteristic pattern corresponding to chagasic patients was ascribed to reactivity with T, cruzi bands of mol. wts 131, 125, 116, 111, 51-45 and 43 kD, that were not recognized by leishmaniasic sera. Trypanosoma cruzi antigens of mol. wts 85, 81, 70, 65 60, 37 and 32kD were considered as crossing antigens, since they were recognized by leishmaniasis sera. With L. mexicana, most of the chagasic patients presented reaction with antigen of mol. wts 124, 107. 92, 59 and 32kD, while bands of mol. wts 155, 140. 73. 56 and 48kD were recognized only by leishmaniasic sera. In this study we found 12 out of 45 sera of patients with leishmaniasis, from a region endemic for both parasitoses, which exhibited a pattern of bands very similar to those corresponding to chagasic individuals, strongly suggesting a mixed infection. This hypothesis was verified by using a purified specific antigen of T. cruzi, Ag163B6, which would be the major cysteine proteinase of this specie (cruzipain). By HLISA, these 12 sera showed a positive reaction with this purified antigen, as those of chagasic patients, thus leading to the confirmation of the presence of a mixed infection.
Serum antibody responses by male and female C57B1/6 mice infected withGiardia muris
Authors: DANIELS C W , BELOSEVIC M 
Published: July 2010

SUMMARYWe compared the levels of serum antibodies in male and female C57BI/6 mice during the primary and after challenge infection with Giardia muris. Male mice began passing cysts in their faeces earlier than females, and were shedding cysts for over 60 days, while females stopped shedding cysts by day 20 after infection. In both males and females there were significant increases in parasite-specific IgM 10 and 20 days after infection. No differences in parasite-specific serum IgA were observed until 40 days after infection. Parasite-specific IgG (whole) levels were elevated on days 20 and 40 in females, while males showed no significant increases. In addition, females had a much stronger IgG2b and IgG3 response than males. After challenge with either cysts or soluble parasite protein only the females had significant increases in specific anti-parasite IgG2b. Our data show differential ability of males and females to control the infection with G. muris is paralleled by a difference in the anti–parasite serum IgG response of the mice.
Immune complex glomerulonephritis is induced in rats immunized with heterologous myeloperoxidase
Authors: YANG J J , JENNETTE J C , FALK R J 
Published: July 2010

SUMMARY
Anti-neutrophil cytoplasmic antibodies (ANCA), including anti-myeloperoxidase (MPO) antibodies, are associated with pauci-immune necrotizing small vessel vasculitis or glomerulonephritis, 1n order to substantiate a pathogenic role for ANCA, an animal model of pauci-immune ANCA-induced glomerulonephritis or vasculitis is required. Brouwer et al. reported pauci-immune glomerulonephritis in rats immunized with human MPO followed by perfusion of kidneys with lysosomal enzyme extract combined with H2O2, and suggested that this could serve as a model of ANCA-induced disease. We repeated these studies in spontaneously hypertensive rats (SHR) and Brown Norway rats (BNR). We immunized rats with human MPO, When circulating anti-MPO antibodies were detectable by indirect immunofluorescence microscopy and ELISA, blood pressure was measured, then perfusion of the left kidney of each rat was done via the renal artery in a closed, blood-free circuit with either MPO + H2O;, MPO, H2O2 alone or MPO + H2O2 neutral protease. Rats were killed on day 4 or day 10 after perfusion, and specimens were examined by light and immunofluorescence microscopy. Pathological lesions and deposits of IgG. C3, and MPO were found in immunized rats perfused with MPO + H2O2 with or without neutral protease, or MPO alone, in both rat strains and on both day 4 and day 10, The degree of histologic injury was proportional in intensity to the amount of IgG immune deposits. Spontaneously hypertensive rats sustained more damage and higher blood pressure than Brown Norway rats. No lesion was observed in immunized rats perfused with H2O2 or in the non-perfused right kidneys. Some of the non-immunized rats perfused with MPO + H2O2 developed pathological lesions. In conclusion, these rat models are examples of immune complex-mediated glomerulonephritis, and therefore are not similar to human ANCA-associated disease.
Quantification and localization of HLA-DR and intercellular adhesion molecule-1 (ICAM-1) molecules on bronchial epithelial cells of asthmatics using confocal microscopy
Authors: VIGNOLA A M , CHANEZ P , CAMPBELL A M , PINELJ A M , BOUSQUET J , MICHEL F-B , GODARD P H 
Published: July 2010

SUMMARYAn increased expression of HLA-DR and lCAM-1 molecules on bronchial epithelial cells has been observed in asthmatic patients. The aim of this study was to evaluate the localization and to quantify the spontaneous expression of HLA-DR and ICAM-1 on bronchial epithelial cells recovered by bronchial brushing of nine asthmatics and nine controls. Epithelial cells constituted over 95% of cells recovered as shown using an anticytokeralin MoAb. Expression of HLA-DR and ICAM-1 was studied using indirect immunofluorescence and confocal microscopy. The intensity of fluorescence of epithelial cells expressing HLA-DR and lCAM-1 was significantly (P&lt; 0·003) increased in asthmatics. In asthmatics, but not in controls, the expression of both molecules was localized in the cytoplasm on the apicolateral portions of the cells. This study shows an up-regulation in the expression of HLA-DR and ICAM-1 molecules by bronchial epithelial cells from asthmatics and a localization of these molecules within the cell.
Intestinal and circulating antibody-forming cells in IgA-deficient individuals after oral cholera vaccination
Authors: FRIMAN V , QUIDING M , CZERKINSKY C , NORDSTRÖM L , LARSSON L , ERICSON D , BJÖRKANDER J , THEMAN K , KILANDER A , HOLMGREN J , HANSON L Å 
Published: July 2010

SUMMARY
In search for a possible explanation for the different susceptibility to mucosal infections in IgA-deficient (IgAd) individuals, the frequency of total immunoglobulin-secreting-ells (ISC) and vaccine-specific antibody-secreting cells (ASC) in intestinal mucosa and peripheral blood was determined by the enzyme-linked immunospot (ELISPOT) assay before and after peroral vaccination with a B subunit-whole cell cholera vaccine. Two groups of IgAd individuals, frequently infected and non-infected respectively, and normal controls were studied. Before cholera vaccination there were significantly higher frequencies of total IgM and IgG ISC in the gut, but not in the blood, in the IgAd individuals than in the controls. However, there were no significant differences between healthy and infection-prone IgAd individuals in this respect. In response to oral cholera vaccination, intestinal cholera toxin (CT)-specific IgG and IgM ASC were significantly more abundant among the IgAd individuals with a history of frequent infections than among ihc healthy IgAd individuals and controls. A similar difference in IgG and IgM ASC, although not significant, was also noted in blood. In IgAd individuals with frequent infections the vaccine induced variable anti-CT IgM ASC responses in the gut, ranging from no increase to a few strikingly high responses. In the controls, the CT-specific responses were dominated by IgA ASC. The data show that oral cholera vaccination evoked strong CT-specific IgG ASC responses, and in some cases also strong IgM ASC responses in the intestinal mucosa of IgAd patients with a history of frequent infections. The healthy IgAd individuals unexpectedly responded with lower numbers of CT-specific IgG ASC and did not show any increase of CT-specific IgM ASC in the intestinal mucosa. Thus, inability to mount a mucosal immune response to an oral antigen cannot in itself explain recurrent infections among many IgAd individuals.
Alveolar macrophages from subjects infected with HIV-1 express macrophage inflammatory protein-1α (MIP-1α): contribution to the CD8+ alveolitis
Authors: DENIS M , GHADIRIAN E 
Published: July 2010

SUMMARYWe examined the synthesis and release of MIP-1α in alveolar macrophages obtained from normal subjects or subjects infected with HIV-1, at different stages of the disease. HIV-1-infected subjects in groups II, III and IV all had significant interstitial pneumonitis, featuring a significant infiltration of CD8+ lymphocytes in the bronchoalveolar lavage. Alveolar macrophages from HIV-1-infected subjects were shown to express significant levels of MIP-1α via immunohistochemistry, both spontaneously and in response to lipopolysaccharide (LPS), whereas cells from normal subjects expressed very low levels of the cytokine. Supernatants of alveolar macrophages from HIV-1-infected subjects exerted strong chemotactic activity for purified activated blood CD8+ T lymphocytes, which was strongly inhibited by neutralizing MIP-1α. Studies of patients with HIV-1 infection at different stages of the disease showed that MIP-1α secretion increased as viral infection developed, There was a significant positive correlation between MIP-1α secretion and the CD8+ alveolitis in HIV-1-infected subjects. Infection of alveolar macrophages in vitro with three distinct strains of HIV-1 which replicated profusely in macrophages did not induce the expression of MIP-1α. Collectively, these data suggest that HIV-1 infection in vivo induces MIP-1α expression and release in alveolar macrophages, and this appears to contribute significantly to the alveolar lymphocytosis seen in HIV-1-infected subjects.
Binding of pentraxins to different nuclear structures: C-reactive protein binds to small nuclear ribonucleoprotein particles, serum amyloid P component binds to chromatin and nucleoli
Authors: PEPYS M B , BOOTH S E , TENNENT G A , BUTLER P J G , WILLIAMS D G 
Published: July 2010

SUMMARYBinding of the human pentraxin plasma proteins, C-reactive protein (CRP) and serum amyloid P component (SAP), to the nuclei of human cells was studied using whole acute phase serum as the source of the proteins and confocal immunofluorescence microscopy. CRP and SAP clearly bound to distinct, different structures. Double staining with MoAbs to the Sm D and Sm B/B′ components of small nuclear ribonucleoproteins confirmed that CRP bound exclusively to these particles. As expected. SAP bound to chromatin and. in addition, binding to the nucleolus was observed for the first time. These interactions demonstrated under relatively physiological conditions, with native pentraxins unseparated from serum and with nuclear constituents in situ, are likely to be of functional importance in vivo.
Endothelial cell activation by tumour necrosis factor-alpha (TNF-α and the development of pre-eclampsia
Authors: MEEKINS J W , McLAUGHLIN P J , WEST D C , McFADYEN I R , JOHNSON P M 
Published: July 2010

SUMMARYPre-eclampsia may develop as a result of an endothelial activation. Tumour necrosis factor-alpha (TNF-α) activates endothelial cells which release soluble E-selectin, a putative circulating marker specific for endothelial damage. A retrospective longitudinal study of maternal blood samples, collected at different gestational ages in pregnancy, was undertaken to determine whether the development of pre-eclampsia is associated with TNF-α-mediated endothelial activation. This study included 19 women who developed pre-eclampsia and 22 women whose pregnancy outcome was normal. Ten women had blood samples taken before pre-eclampsia was clinically detected and, in all these, TNF-α was below the immunoassay limit of detection (&lt; 80 pg/ml). Five had further samples taken after pre-eclampsia was clinically diagnosed and, initially, TNF-α was still below the lower limit of detection in all five pregnancies, but rose later in three (80, 156 and 250 pg/ml). In nine other patients with diagnosed pre-eclampsia, TNF-α was detected in only two (80 and 650 pg/ml). TNF-α was identified in only one of the 22 normal pregnancies (80 pg/ml), this being at term. There was no statistical difference in soluble E-selectin levels between normal and pre-eclamptic pregnancies, neither before nor after pre-eclampsia was diagnosed. Hence, blood TNF-α levels measured by immunoassay can be elevated in approximately 36% of cases of established preeclampsia, but this rise occurs only after the syndrome is detected clinically. Blood concentrations of TNF-α and soluble E-selectin are not related to severity of the disorder. These findings suggest that circulating TNF-α does not contribute to the initiation of endothelial cell activation that may be associated with the development of pre-eclampsia, but may rise as a consequence of the pathological processes of this disorder.