Complement (Basel, Switzerland)最新文献

{"title":"Formation of covalent complexes between the fourth component of human complement and IgG immune aggregates.","authors":"J M Alcolea,&nbsp;L C Antón,&nbsp;G Marqués,&nbsp;P Sánchez-Corral,&nbsp;F Vivanco","doi":"10.1159/000463004","DOIUrl":"https://doi.org/10.1159/000463004","url":null,"abstract":"<p><p>The binding properties of activated C4 to immune complexes (ovalbumin-rabbit IgG antiovalbumin) were studied by using 125I-IgG in the immune complexes or performing the C4 binding assays in the presence of 14C-iodoacetamide. High molecular weight complexes formed between C4 and IgG could be detected by the incorporation of 14C-iodoacetamide in the -SH group generated in the nascent C4b during the activation process. The same complexes with an apparent molecular weight of 180,000 daltons were detected when the immune aggregates contained 125I-IgG. Two-dimensional SDS-PAGE analysis of the C4b-IgG covalent complexes indicated: In the absence of control proteins, the complexes are formed by the alpha'-chain of C4b and the H chain of the antibody. The alpha'-H complexes are 36% sensitive to hydroxylamine and 64% resistant. This is consistent with the presence of two populations of C4, which are not equivalent in their covalent binding with immune complexes. Covalent complexes C4-C4b or C4b(like)-C4b(like) are generated during the C4 activation and they are detected as alpha-alpha' or alpha-alpha complexes, respectively. Interaction of C4b with the L chain of the antibody molecule also seems to occur, but to a lesser extent than with the H chain.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"4 1","pages":"21-32"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000463004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14690559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of complement receptor type three and serum opsonins in the neutrophil response to yeast.","authors":"J A Cain,&nbsp;S L Newman,&nbsp;G D Ross","doi":"10.1159/000463011","DOIUrl":"https://doi.org/10.1159/000463011","url":null,"abstract":"<p><p>Previous studies have suggested that neutrophil complement receptor type three (CR3) has two binding sites: (1) a site for fixed iC3b that does not trigger ingestion or a superoxide (O2-) burst, and (2) a function-triggering site for the beta-glucan component of yeast (Saccharomyces cerevisiae) cell walls. In the present study it was found that yeast (Y) coated with C3b (YC3b) or iC3b (YC3bi), prepared with purified complement in an IgG-free system, were avidly ingested ans stimulated a vigorous O2- burst, whereas sheep erythrocytes (E) bearing C3b or iC3b, were not ingested and did not give an O2- burst. YC3b and YC3bi contained an amount of fixed C3 that was approximately equal to serum-opsonized Y (OY), and produced O2- bursts comparable to OY. Experiments utilizing rabbit F(ab')2 anticomplement receptor type one (anti-CR1) to block fixed C3b binding to CR1, and monoclonal anti-CR3 (MN-41 or OKM1) to block fixed iC3b and Y cell wall binding to CR3, indicated that the O2- burst response to OY was primarily due to fixed iC3b and Y cell wall binding to CR3. Fixed C3b (that represented 33% of the fixed C3 on OY) and IgG anti-Y antibodies that bound to CR1 and Fc receptors, respectively, were found to contribute little to the response. Although YC3b did bind avidly to neutrophil CR1, the results suggested that the O2- burst response to YC3b was triggered after the initial YC3b binding by the secondary attachment of Y cell wall components to CR3. When neutrophils were treated with anti-CR3, 90% of neutrophils bound YC3b (via CR1), but phagocytosis and an O2- burst were completely absent. Similar findings were made with OKM1-treated neutrophils and YC3bi. Responses of OKM1-treated neutrophils were inhibited because only the iC3b-binding site of CR3 was ligated by the YC3bi. Thus, fixed C3b or iC3b on Y mediate avid binding of Y to neutrophils via CR1 or the iC3b-binding site of CR3, respectively, but ingestion and an O2- burst response are only triggered when glucans in the Y cell wall secondarily bind to neutrophils via the beta-glucan binding site of CR3.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"4 2","pages":"75-86"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000463011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14172380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunopharmacology of anaphylatoxin-induced bronchoconstrictor responses.","authors":"N P Stimler-Gerard","doi":"10.1159/000467891","DOIUrl":"https://doi.org/10.1159/000467891","url":null,"abstract":"<p><p>The complement anaphylatoxin peptides, C3a and C5a, are potential mediators of immediate hypersensitivity reactions, eliciting many of the same actions on isolated tissue and cell preparations as specific antigen. Instilled intratracheally in experimental animals, the peptides induce acute bronchospasms and are sometimes lethal. In vitro, they cause dose-dependent contraction of isolated lung tissue preparations, a response which correlates well with bronchospasms observed in vivo, and our current understanding of the cellular and molecular mechanisms of this action are reviewed here. C5a and its catabolic derivative, C5ades Arg, stimulate contraction of isolated guinea pig lung parenchymal strips in part by production of leukotrienes that constitute SRS-A, and by release of histamine. Leukotrienes in turn release thromboxane from lung tissue, and evidence indicates that at least part of the spasmogenic activity of these peptidolipids is mediated by this effect. C3a is considerably less potent than C5a in contracting lung tissues and appears to act primarily by causing the release of spasmogenic cyclooxygenase metabolites. Both peptides may additionally have direct action on contractile cells within the tissue. Platelet-activating factor (PAF), an unusual phospholipid mediator released from inflammatory cells stimulated with C5a and other agents, also contracts isolated lung parenchymal tissues. PAF stimulates release of significant quantities of thromboxane from guinea pig lung; however, indomethacin does not block contractile responses of the tissue. Recent evidence indicates that PAF may act on parasympathetic neurons in lung to release endogenous acetylcholine, and this action may be a major component of tissue responses to this mediator. Thus the complement anaphylatoxins stimulate release of many of the same mediators from lung tissues as are released by antigen challenge of sensitized tissue, and may, therefore, play an important role in the pathogenesis of allergic bronchospasms.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 3","pages":"137-51"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467891","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14159745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of the immune response by anaphylatoxins.","authors":"E L Morgan","doi":"10.1159/000467890","DOIUrl":"https://doi.org/10.1159/000467890","url":null,"abstract":"Bioactive C3a and C5a fragments derived from the human complement compounds C3 and C5, respectively, possess immunoregulatory activities. C3a and C5a differentially influence in vitro immune function. C3a was found to be a potent suppressor of antigen-specific and polyclonal antibody responses. In contrast, C3a was unable to suppress antigen-or mitogen-induced B and T cell proliferation. Analyses of synthetic peptides based on the sequences of C3a revealed that the carboxy-terminal region of the molecule is responsible for immunosuppression. C3a-mediated suppression occurs through the activation of a nonspecific suppressor T cell pathway. In contrast to the results obtained with C3a, C5a was found to augment both in vitro humoral and cell-mediated immune responses. Regulation of immune function by complement components may form part of an in vitro nonspecific immunoregulatory network.","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 3","pages":"128-36"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467890","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14664808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical utility of complement anaphylatoxin assays.","authors":"D E Hammerschmidt","doi":"10.1159/000467893","DOIUrl":"https://doi.org/10.1159/000467893","url":null,"abstract":"<p><p>Meaningful quantitation of complement activation is difficult by conventional techniques, because of the dynamic equilibrium status of complement components. Assays for complement-derived split products have been useful adjuncts, but until recently have been cumbersome and only semiquantitative. The recent introduction of superior assay methods, especially immunoassays for the complement derived anaphylatoxins, has enhanced such study by allowing more sensitivity, specificity and reproducibility. Such assays are already being applied to the study of diseases in which complement activation may play a role, as well as to the evaluation of biocompatibility of various prosthetic materials and drugs. 'Beside' clinical utility of the tests is still limited, but may grow rapidly if assays are devised which are capable of more rapid and less expensive performance.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 3","pages":"166-76"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467893","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14664809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Site-specific activation of the alternative pathway of complement. Synthesis of a hybrid molecule consisting of antibody and cobra venom factor.","authors":"C. Parker, V. F. White, R. Falk","doi":"10.1159/000467900","DOIUrl":"https://doi.org/10.1159/000467900","url":null,"abstract":"Cobra venom factor (CoF) is an analog of the activated third component of human complement (C3b). Unlike C3b, CoF is completely resistant to inactivation by factors H and I, the endogenous control proteins of the alternative pathway of complement. This property makes CoF a useful reagent when unrestricted activation of complement is desired. CoF was covalently conjugated to the IgG fraction of rabbit antihuman erythrocyte antiserum, and the ability of the hybrid molecules to initiate activation of the alternative pathway at a specific site was tested. The hybrid molecules were heterogeneous polymers (CoFn-IgGn, where n is an integer greater than 1 for at least one of the components), and both components retained their individual functional activities. The alternative-pathway C3/C5 convertase complex was formed by adding purified factors B and D to the hybrid in the presence of magnesium. This complex (antibody-CoFBb) was able to bind to erythrocytes and activate both C3 and C5. Activation of C5 initiated formation of the potentially cytolytic membrane attack complex of complement on the surface of the cell. When used in combination with rabbit serum, the hybrid molecule was a potent mediator of complement-induced hemolysis. The decay kinetics of the hybrid C3/C5 convertase complex when bound to normal human erythrocytes were not first order, but 40% of the activity remained after 3.5 h at 37 degrees C. Conjugation of CoF to specific antibodies will permit investigation of the consequences of alternative-pathway activation at selective sites. These hybrids may also have therapeutic potential.","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 4 1","pages":"223-35"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467900","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65234476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Normal distribution of complement C3b receptor (CR1) numbers on erythrocytes in blood donors: low levels are associated with HLA-B27.","authors":"B S Thomsen,&nbsp;S E Jacobsen,&nbsp;H Nielsen,&nbsp;B K Jakobsen,&nbsp;H Sørensen","doi":"10.1159/000467883","DOIUrl":"https://doi.org/10.1159/000467883","url":null,"abstract":"<p><p>Blood donors were examined for C3b receptor (CR1) levels on erythrocytes by a microtiter plate enzyme-linked immunosorbent assay and for HLA-A, -B, and -C antigens, C3 phenotypes and blood groups. The CR1 levels among 150 donors varied in the range from 24 to 130% (mean +/- 1 SD = 69.9 +/- 22.9) of an erythrocyte standard, and in accordance with a polygenic model of inheritance the distribution of CR1 was well approximated by a normal curve (chi-square goodness-of-fit test nonsignificant, p = 0.66). Low CR1 levels were associated with HLA-B27 (n = 11, p = 0.05), which was confirmed by investigation of further 20 HLA-B27-positive donors (p = 0.05). The CR1 levels were not associated with a certain C3 phenotype. Possibly, the blood group phenotype M-M + S-s+ is associated with high and the S antigen with low CR1 numbers. The relation between low CR1 numbers and HLA-B27 might be important for the understanding of the association between HLA-B27 and certain inflammatory rheumatological diseases.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 2","pages":"79-87"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467883","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14082032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anaphylatoxin formation in extracorporeal circuits.","authors":"D E Chenoweth","doi":"10.1159/000467892","DOIUrl":"https://doi.org/10.1159/000467892","url":null,"abstract":"<p><p>Anaphylatoxin radioimmunoassay techniques have been employed to define both the temporal profile and the amount of complement activation taking place in two different types of extracorporeal circuits. Prospective studies of patients undergoing both maintenance hemodialysis and cardiopulmonary bypass provided essentially similar findings. In both cases, plasma C3a antigen levels proved to be the most accurate and sensitive indicator of intravascular complement activation. By contrast, plasma C5a levels varied little during the period of extracorporeal circulation. Instead, this anaphylatoxin retained considerable biologic activity in vivo as evidenced by its ability to promote granulocyte activation and transient granulocytopenia which was displayed by patients in both groups. Plasma levels of C4a antigen were not elevated during the period of extracorporeal circulation, suggesting that alternative pathway mechanisms were predominantly responsible for the complement activation taking place in both hemodialyzers and bypass oxygenators. However, classical pathway activation events could be documented when protamine sulfate was administered to heparinized patients after cardiopulmonary bypass. In this instance, elevated plasma levels of both C4a and C3a antigens were observed. Prospective studies also suggested that complement activation could be associated with the development of both acute and delayed clinical sequelae. Available data support the hypothesis that C5a anaphylatoxin might be the primary mediator of these undesirable effects of extracorporeal circulation. These types of investigations have contributed significantly to our understanding of the role of the anaphylatoxins in human disease and may be directly applied to facilitate design of more biocompatible medical devices.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 3","pages":"152-65"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467892","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14616046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breakdown of C3 covalently bound to F(ab')2 immune complexes after complement activation by the alternative pathway.","authors":"L C Antón,&nbsp;J M Alcolea,&nbsp;G Marqués,&nbsp;P Sánchez-Corral,&nbsp;F Vivanco","doi":"10.1159/000467881","DOIUrl":"https://doi.org/10.1159/000467881","url":null,"abstract":"<p><p>The activation and subsequent degradation of C3 covalently bound to immune complexes (IC) has been studied by using immune aggregates antiovalbumin-125I-F(ab')2-ovalbumin or 125I-C3 in the presence of serum. Kinetic experiments were performed in order to establish the physiological sequence of C3 degradation as a function of time. The results indicated: The interaction C3-IC, as analyzed in SDS-PAGE, results in bands of high molecular weight corresponding to C3 alpha-65-Fd and C3 alpha-41-Fd covalent complexes. In the first 7 min only C3 alpha-65-Fd complexes were detected. From 7 to 15 min a progressive increase in the C3 alpha-41-Fd complexes occurs. After this time the ratio C3 alpha-65-Fd/C3 alpha-41-Fd was kept constant for at least 45 min. Hence, C3b covalently bound to F(ab')2 IC is degraded in serum much faster than when it is bound to IgG IC. The spatial distribution of the Fab arms in the IC appears to be a critical feature in providing a protective environment for C3b. The orientation of the Fab arms was dependent on the presence of the Fc regions.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 2","pages":"53-62"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467881","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14887025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased expression of C3b receptor (CR1) on erythrocytes of patients with systemic lupus erythematosus contrasts with its normal expression in other systemic diseases and does not correlate with the occurrence or severity of SLE nephritis.","authors":"M H Jouvin,&nbsp;J G Wilson,&nbsp;P Bourgeois,&nbsp;D T Fearon,&nbsp;M D Kazatchkine","doi":"10.1159/000467884","DOIUrl":"https://doi.org/10.1159/000467884","url":null,"abstract":"<p><p>Expression of the C3b/C4b receptor (CR1) on erythrocytes is decreased in patients with systemic lupus erythematosus (SLE) compared to normal individuals, and the CR1 antigen is absent from podocytes in severe diffuse proliferate nephritis of SLE. In the present study, we examined the relationship between the number of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes in non-SLE nephritis and other systemic inflammatory diseases by measuring the binding of 125I-labeled rabbit F(ab')2 and murine monoclonal IgG anti-CR1 antibodies to erythrocytes of normal individuals and patients in a French population. The number of binding sites for monoclonal anti-CR1 antibody on erythrocytes of 116 normal individuals was 743 +/- 22 (mean +/- SEM) with a range of 169-1,333, and the frequency distribution of this number in the population was bimodal. In 112 patients with SLE, the mean number of CR1 sites on erythrocytes was decreased to 62% of the mean for normal individuals (p less than 0.001). No correlation was found between CR1 expression on erythrocytes and the presence or immunohistopathological type of glomerulonephritis in biopsy specimens from these patients. The mean number of CR1 on erythrocytes of 29 patients with non-SLE glomerulonephritis was slightly decreased to 89% of the normal mean (p greater than 0.05), which could not be attributed to glomerular immune complex disease or vasculitis.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 2","pages":"88-96"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467884","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14082035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}