Search results for "Complement system"
showing 10 items of 157 documents
Generation of chemotactic activity by immune complexes carrying clustered or nonclustered C&42horbar; sites
1973
Sensitized cells (EA) bearing different numbers of &42horbar; sites were tested for their ability to generate chemotactic activity from C-EDTA. From the results it can be shown that: 1 the amount of chemotactic activity generated parallels the number of &42horbar; sites bound to the cell surface, 2 all &42horbar; sites clustered around a single hemolytic site are enzymatically active as far as generation of chemotactic activity is concerned, and, 3 no difference can be demonstrated with IgG or IgM antibodies
An inherited deficiency of the third component of complement, C3, in guinea pigs
1986
Hereditary deficiency of the third component of complement, C3, is found very seldom in the human. C3 deficiency is associated with severe bacterial infections revealing the central role of C3 in complement activation via the classical or alternative pathway. We describe a new hereditary C3 deficiency in strain 2 guinea pigs. Serum from these animals had a markedly reduced lytic activity in a standard assay for complement-dependent, antibody-mediated cytotoxicity. In functional assays of individual components, the hemolytic activity of the components C4, C2, C5 and of factors B, D and H was in the normal range. The functional C3 titer, and similarly C3 antigenic activity in the serum of the…
Functionally active complement proteins C6 and C7 detected in C6- and C7-deficient individuals
1991
SUMMARYTwo sensitive sandwich ELISAs based on monoclonal antibodies directed to native C6 and C7 allowed the detection and quantitation of these complement proteins in 20 out of 37 serum samples from individuals who had previously been classified as deficient in these proteins as assessed by immunochemical and/or functional assays. Furthermore, serum from four C6-deficient and one combined C6-/C7-deficient individual showed an increase in the terminal complement complex (TCC) and a decrease in native C6 and C7 after complement activation as assayed by specific ELISAs. Despite their (incomplete) deficiencies, these individuals therefore possess functionally active terminal complement protein…
Comparative study on biological activities of various anaphylatoxins (C4a, C3a, C5a)
1981
Several anaphylatoxic substances (human C3a, guinea pig C3a, human C4a, guinea pig C5a, and a synthetic C3a-related hexapeptide) were compared with regard to their ability to induce secretion of [3H] serotonin from guinea pig platelets. Functional identity of the C3a preparations, C4a, and the hexapeptide was demonstrated by the phenomenon of crossed desensitization. Whereas C3a of human and guinea pig origin proved to be qualitatively and quantitatively identical, C4a expressed only 3% of the activity of the C3 fragments on a molar basis. Investigations with goat anti-guinea pig C3a demonstrate that human and guinea pig C3a possess one antigenic determinant in common; however, this determi…
Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherap…
2015
The efficacy of antibody-based immunotherapy is due to the activation of apoptosis, the engagement of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC). We developed a novel strategy to enhance CDC using bispecific antibodies (bsAbs) that neutralize the C-regulators CD55 and CD59 to enhance C-mediated functions. Two bsAbs (MB20/55 and MB20/59) were designed to recognize CD20 on one side. The other side neutralizes CD55 or CD59. Analysis of CDC revealed that bsAbs could kill 4-25 times more cells than anti-CD20 recombinant antibody in cell lines or cells isolated from patients with chronic lymphocytic leukemia. The pharmacokinetics of the bsAbs was evaluate…
C1-esterase inhibitor in ischemia and reperfusion.
2002
Summary Myocardial injury from ischemia can be aggravated by reperfusion of the jeopardized area. The precise underlying mechanisms have not been clearly defined, but proinflammatory events including complement activation play important roles. Cardioprotection by complement inhibition inter alia C1-esterase-inhibitor (C1-INH) was examined in several experimental models and under clinical conditions with ischemia and reperfusion. C1-INH reduced local anaphylatoxin release revealing the importance of the classical complement pathway. Inhibition of local complement activation was accompanied by improvement of myocardial function and perfusion of the previously ischemic myocardium. Leukocyte en…
A novel cholinergic-specific antigen (Chol-2) in mammalian brain.
1993
Three new antisera have been raised in sheep against cholinergic electromotor presynaptic plasma membranes prepared from the electric organs of the electric ray, Torpedo marmorata. They all recognized one or more cholinergic-specific antigens in the mammalian nervous system by the following criteria: they sensitized the cholinergic subpopulation of rat-brain synaptosomes--and only this subpopulation--to lysis by the complement system and, in an immunocytochemical study, selectively stained choline acetyltransferase-positive cholinergic neurons in the rat spinal cord. However, two of the three antisera failed to recognize Chol-1 alpha and -beta, two closely related minor gangliosides already…
Studies on the mechanism of PMN activation. I. By dextran sulfates.
1982
Evidence is presented that enhanced reduction of the dye nitroblue-tetrazolium (NBT) by polymorphonuclear leukocytes (PMN) which are stimulated by dextran sulfates (DS) is not exclusively due to the phagocytosis of particles formed by NBT and DS. Not only the size of phagocytizable particles but the degree of substitution determines the acceleration of NBT-reduction. A likely cause of this acceleration is the triggering of the alternative pathway of the complement activation.
C1q secreted in the tumour microenvironment promotes tumour growth in the absence of complement activation
2012
We have recently shown that locally secreted C1q is involved in trophoblast invasion of decidua during pregnancy (Agostinis et al., J. Immunol. 2010;185;4420–4429). Since this physiologic process resembles to some extent tumor progression, we sought to investigate if C1q plays a similar role in tumor development and progression. Immunohistochemical analysis of several solid tumours including colon, prostate, lung and breast cancer and melanoma revealed the presence of C1q that was localized on the vascular endothelium and also distributed in the stroma in the absence of C4. To investigate the in vivo role of C1q in tumour development, 6/8 week old female WT and C1q−/− C57BL/6 mice received …
Binding and activation of human and mouse complement by Cryptosporidium parvum (Apicomplexa) and susceptibility of C1q- and MBL-deficient mice to inf…
2008
Cryptosporidium parvum is a protozoan parasite (Apicomplexa) that causes gastrointestinal disease in animals and humans. Whereas immunocompetent hosts can limit the infection within 1 or 2 weeks, immunocompromised individuals develop a chronic, life-threatening disease. The importance of the adaptive cellular immune response, with CD4+ T-lymphocytes being the major players, has been clearly demonstrated. Several non-adaptive immune mechanisms have been suggested to contribute to the host defence, such as interferon-gamma (IFN-gamma) from NK cells, certain chemokines, beta-defensins and pro-inflammatory cytokines, but the influence of the complement systems has been less well studied. We ana…