Antibody-independent activation of C1. II. Evidence for two classes of nonimmune activators of the classical pathway of complement

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Serval ID
serval:BIB_12C412049A39
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antibody-independent activation of C1. II. Evidence for two classes of nonimmune activators of the classical pathway of complement
Journal
Journal of Immunology
Author(s)
Peitsch  M. C., Kovacsovics  T. J., Tschopp  J., Isliker  H.
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
03/1987
Volume
138
Number
6
Pages
1871-6
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar 15
Abstract
Nonimmune activation of the first component of complement (C1) by cardiolipin (CL) vesicles present specific features which were not demonstrated on immune complexes. CL vesicles which activate C1 in the presence of C1-inhibitor (C1-INH) were found to bind C1s in the absence of C1r, and to induce a specific C1r-independent cleavage of C1q-bound C1s. Therefore, several known natural nonimmune activators were analyzed by comparing their ability to activate C1 in the presence of C1-INH and to mediate a C1r-independent cleavage of C1s. Freshly isolated human heart mitochondria (HHM) activated C1 only in the absence of C1-INH. However, mitoplasts derived from HHM (HHMP) activated C1 regardless of the presence of C1-INH, and induced a specific cleavage of C1q-bound C1s. The same pattern was observed in the case of smooth E. coli and a semi-rough E. coli strain. DNA, known to activate C1 only in the absence of C1-INH, does not induce C1s cleavage in the absence of C1r. Thus, nonimmune activators can be classified into two distinct categories. "Strong" activators, such as CL vesicles, HHMP, or the semi-rough E. coli strain J5 can activate C1 in the presence of C1-INH. By using C1qs2 as a probe, they exhibit a specific, C1r-independent cleavage of C1s. C1s-binding to C1q is a critical factor for the activation process in this group. In the case of "weak" activators, such as E. coli smooth strains, DNA, or HHM, no C1s-binding to activator-bound C1q was detected, and C1r-independent C1s cleavage and C1 activation in the presence of C1-INH were not observed. As in the case of immune complexes, C1r activation appears to play a key role in the C1 activation by "weak" activators.
Keywords
Calcium/metabolism Cardiolipins/*immunology Complement Activating Enzymes/immunology *Complement Activation Complement C1/*immunology Complement C1 Inactivator Proteins/immunology Complement C1q Complement C1r Complement C1s Complement C2/immunology Complement C4/immunology *Complement Pathway, Classical Escherichia coli/immunology Humans Mitochondria, Heart/immunology
Pubmed
Web of science
Create date
24/01/2008 15:18
Last modification date
20/08/2019 12:41
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