Possible mechanisms of degradation of C1q in vivo and in vitro: role of macrophages.
Low levels of C1q may be found in sera of patients with diseases such as systemic lupus erythematosus, serum sickness and bacterial endocarditis. In vitro, C1q can be bound by immune complexes and induce activation of the proenzymes C1r and C1s, resulting in an activated C1 molecule. In the presence of C1-In in the reaction mixture C1r and C1s are dissociated rapidly from the immune complex-bound C1q. This C1q has the possibility to interact with free precursor C1r and C1s to form a new C1 molecule at the surface of the immune complex and induce a new cycle of activation. In vivo, however, such a possibility does not seem to play a major role, because low levels of C1q are found in various diseases which are thought to be mediated by immune complexes. Therefore we studied the clearance rate of C1q in rats in the presence and absence of soluble aggregates of IgG (AIgG). It was found that 125I-C1q is cleared from the circulation of rats with a halflife of 12.4 hrs and increasing concentrations of AIgG enhanced the clearance of 125I-C1q in vivo. Studies in which various organs were analyzed for 125I-C1q indicated that the liver is the main site of clearance and that the Kupffer cells seem to play a major role. These, and other in vitro studies, indicate that in vivo complement activation, may contribute to a higher degree of turnover of C1q in vivo and cause depletion of circulating C1q.(ABSTRACT TRUNCATED AT 250 WORDS)
Daha
M R
MR
Department of Nephrology, University Hospital Leiden, The Netherlands.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D015922:Complement C1q / Q000378:metabolism*; D003171:Complement Pathway, Classical; D006168:Guinea Pigs; D006801:Humans; D007105:Immune Complex Diseases / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051381:Rats
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015922:Complement C1q