{"title":"Activation of the alternative pathway of complement by DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (Mergetpa).","authors":"I von Zabern, R Nolte","doi":"10.1159/000467885","DOIUrl":"https://doi.org/10.1159/000467885","url":null,"abstract":"<p><p>Incubation of normal human serum with 3-5 mM Mergetpa causes activation of the alternative pathway of complement as indicated by fragmentation of C3 and factor B, dependent on the presence of divalent cations. Mergetpa inhibits the regulatory protein factor I and, as a consequence, may allow initiation of the feedback cycle of the alternative pathway by deregulation. The classical pathway is not or only to a minor extent activated. A decrease in the hemolytic activity of C2, C5 and one or several of the components C6-9 in the presence of 5 mM Mergetpa may be explained by direct inactivation. The described effects are probably mediated by Mergetpa acting as a thiol.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 2","pages":"97-104"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14225989","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":"A sensitive ELISA for the quantitation of human C5a in blood plasma using a monoclonal antibody.","authors":"M Schulze, O Götze","doi":"10.1159/000467875","DOIUrl":"https://doi.org/10.1159/000467875","url":null,"abstract":"<p><p>An ELISA for the quantitation of the C5a anaphylatoxin of complement in human plasma is presented which is based on the use of both a monoclonal antibody and polyclonal antibodies to C5a. Its detection limit is 1 ng C5a/ml plasma. It detects no C5a in fresh EDTA-plasma. Complete removal of C5 by an optimized precipitation step prior to the assay procedure is an essential feature of the method.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 1","pages":"25-39"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14861636","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":"Anaphylatoxins: possible roles in disease.","authors":"W Vogt","doi":"10.1159/000467894","DOIUrl":"https://doi.org/10.1159/000467894","url":null,"abstract":"<p><p>Anaphylatoxins, in particular C3a and C5a, have various biological activities which suggest a role as mediators of inflammatory reactions: they cause contraction of smooth muscle, histamine release, increase in capillary permeability, adhesion of leukocytes to vascular endothelium, leukocyte chemotaxis, and aggregation of platelets and leukocytes. Most of these effects are supported by the cooperation of other mediators, in particular arachidonic acid derivatives which may be produced by anaphylatoxin-stimulated cells, e.g. leukocytes or endothelium. In vivo effects of the complement peptides depend very much on the site of their generation: intravascular release in the general circulation leads to adverse symptoms such as adult respiratory distress syndrome and shock lung, mainly due to leukocyte activation, aggregation and their accumulation in lung vessels. Intravascular release may be induced by certain drugs, and by contact of blood with the surfaces of bypass or dialysis apparatus. Induction of local inflammatory and defense reactions requires release of anaphylatoxins in tissue spaces. Tissue fluid differs quantitatively from blood plasma in its concentration of complement components. This raises some problems of how efficient concentrations of C3a and C5a can be attained at the site of a lesion to generate a chemotactic gradient capable of attracting blood leukocytes.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 3","pages":"177-88"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467894","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14159746","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":"Biochemistry and biology of anaphylatoxins.","authors":"T E Hugli","doi":"10.1159/000467889","DOIUrl":"https://doi.org/10.1159/000467889","url":null,"abstract":"<p><p>The molecular architecture of anaphylatoxins has been explored on several levels. Primary, secondary and tertiary structural parameters that dictate function of the C3a, C4a and C5a molecules are being elucidated with the aid of comparative sequence analyses, physical measurements and organic syntheses. Although C3a, C4a and C5a are biologically distinct mediators, as defined by their unique receptor systems, a common genetic origin is apparent from conserved features in their primary structures. Evidence is now available which suggests that similarities in the folding pattern of the anaphylatoxins may dictate a concensus conformation for each factor. We have learned from synthetic peptide studies that the binding (e.g. effector) site in anaphylatoxin molecules exists as a linear sequence contained in the C-terminal portion of the polypeptide. What is also evident is that a preferred conformation is defined for the binding site requiring a proper side chain orientation for optimal bioactivity. It is proposed that folding of the native structure stabilizes this conformation at the binding site. The binding site in C3a contains the essential residues LGLAR folded in an irregular or pseudo-beta-turn and stabilized by an adjacent alpha-helical segment. It is proposed that the alpha-helical segment influences orientation of the side chain residues in the 'binding site'. A similar model is evolving for C5a based on synthetic C5a peptides that express both spasmogenic and chemotactic activities. This helix turn model promises to be representative of an essential structural feature that determines anaphylatoxin activity. We believe that these models contribute significantly to our understanding of the molecular relationships between structure and function for these humoral mediators of inflammation.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 3","pages":"111-27"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467889","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14664807","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}
V M Holers, T Seya, E Brown, J J O'Shea, J P Atkinson
{"title":"Structural and functional studies on the human C3b/C4b receptor (CR1) purified by affinity chromatography using a monoclonal antibody.","authors":"V M Holers, T Seya, E Brown, J J O'Shea, J P Atkinson","doi":"10.1159/000467882","DOIUrl":"https://doi.org/10.1159/000467882","url":null,"abstract":"<p><p>A procedure was devised that has several advantages over previously described methods to purify CR1 from both erythrocytes (E) and the HL-60 promyelocytic cell line. Using a monoclonal antibody immunoaffinity column, CR1 was purified to homogeneity as assessed by silver staining and 2-D gel analysis. Protein purified by this method comigrates on SDS-PAGE with 125I surface-labeled CR1 isolated by immunoprecipitation or iC3-Sepharose affinity chromatograhy and can be specifically immunoblotted with a second monoclonal anti-CR1 antibody. Employing this method, CR1 can be purified to homogeneity in amounts adequate for both functional studies and biochemical microanalysis. Purified E CR1 is functionally active as assessed by its ability to specifically rebind to an iC3-Sepharose affinity column, act as a cofactor for I-mediated cleavage of C3b to C3c and C3d, g and to accelerate decay of both the classical and alternative pathway C3 convertases. Its specific activity is similar to that of CR1 purified by a method not employing the potentially denaturing washing and eluting conditions of immunoaffinity chromatography. The pIs of the two major E CR1 allotypes are both approximately 7.1. Using pooled human E CR1, an amino acid composition was derived which revealed a relatively high proline content. This has also been found in two functionally related and genetically linked complement-regulatory proteins, H and C4-binding protein, NH2-terminal sequencing of E CR1 and HL-60 CR1 was unsuccessful indicating that the NH2-terminus is blocked.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 2","pages":"63-78"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467882","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14082031","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}
S S Asghar, K P Dingemans, A Kammeijer, W R Faber, M Y Abdel Mawla
{"title":"Suppression of complement-mediated vascular injury at Arthus reaction sites by complement inhibitors.","authors":"S S Asghar, K P Dingemans, A Kammeijer, W R Faber, M Y Abdel Mawla","doi":"10.1159/000467876","DOIUrl":"https://doi.org/10.1159/000467876","url":null,"abstract":"<p><p>Certain complement inhibitors, namely chlorpromazine, suramin, 2-hydroxystilbamidine and chlorophenothiazine sulphonate were tested for their ability to suppress complement deposition and vascular injury at the site of an Arthus reaction. Deposition of complement was suppressed in the order 2-hydroxystilbamidine greater than suramin greater than chlorpromazine. All the above mentioned four compounds strongly protected vascular injury as observed by electron microscopic studies. At Arthus reaction sites prepared without drug treatment venules ranged from normal to severely altered and damaged. Discontinuities in endothelial linings varied from small to longer stretches. In the latter situation remaining endothelial cells were degenerated and endothelial remnants did not have an intact basal lamina. After treatment with the above complement inhibitors, at arthus reaction sites some venules appeared normal, whereas others were altered but in all cases the endothelium and its basal lamina remained intact.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 1","pages":"40-8"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14078211","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":"Imbalance between polymorphonuclear leukocyte proteases and antiproteases in chronic pyogenic infections and its relation to the proteolysis of complement component C3.","authors":"S Suter","doi":"10.1159/000467874","DOIUrl":"https://doi.org/10.1159/000467874","url":null,"abstract":"","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 1","pages":"1-24"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14650690","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 J Parker, V F White, R J Falk","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 4","pages":"223-35"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14763490","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":"European Meeting on Complement in Human Disease. September 3-5, 1986, Veszprém (Lake Balaton), Hungary.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"3 4","pages":"189-222"},"PeriodicalIF":0.0,"publicationDate":"1986-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14921624","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":"Early- and late-phase activation of complement evaluated by plasma levels of C3d,g and the terminal complement complex.","authors":"T E Mollnes","doi":"10.1159/000467856","DOIUrl":"https://doi.org/10.1159/000467856","url":null,"abstract":"<p><p>Activation of the initial part (early phase) and terminal part (late phase) of the complement cascade was examined. C3d,g and the fluid-phase terminal complement complex were quantified and compared after spontaneous in vitro activation and after acute in vivo activation caused by extracorporeal circulation during coronary artery surgery. The results suggest that there is a close but not complete correlation between early- and late-phase activation of complement, that C3d,g and the terminal complement complex have different elimination rates in vivo, and that these two indicators are valuable for evaluation of early- and late-phase activation, respectively.</p>","PeriodicalId":77697,"journal":{"name":"Complement (Basel, Switzerland)","volume":"2 2-3","pages":"156-64"},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000467856","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14995523","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}