C5a anaphylatoxin as a product of complement activation up-regulates the complement inhibitory factor H in rat Kupffer cells

European Journal of Immunology
G SchlafO Götze

Abstract

The 155-kDa complement regulator factor H (FH) is the predominant soluble regulatory protein of the complement system. It acts as a cofactor for the factor I-mediated conversion of the component C3b to iC3b, competes with factor B for a binding site on C3b and C3(H2O) and promotes the dissociation of the C3bBb complex. The primary site of synthesis is the liver, i.e. FH-specific mRNA and protein were identified in both hepatocytes (HC) and Kupffer cells (KC). Previous studies in rat primary HC and KC had shown that the proinflammatory cytokine IFN-gamma influences the balance between activation and inhibition of the complement system through up-regulation of the inhibitory FH. In this study we show that C5a, as a product of complement activation, stimulates the expression of FH-specific mRNA and protein in KC and thus induces a negative feedback. Quantitative-competitive RT-PCR showed an approximate threefold C5a-induced up-regulation of FH. ELISA analyses revealed a corresponding increase in FH protein in the supernatants of KC. The up-regulation of FH was completely inhibited by the C5a-blocking monoclonal antibody 6-9F. Furthermore, an involvement of LPS and IFN-gamma was excluded, which strongly indicates a direct effect of...Continue Reading

References

Nov 2, 1976·The Journal of Experimental Medicine·K Whaley, S Ruddy
May 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·M K Pangburn, H J Müller-Eberhard
Sep 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·J M WeilerD T Fearon
Jan 15, 1992·The Biochemical Journal·D F LappinK Whaley
May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S Meri, M K Pangburn
Jan 1, 1989·Advances in Immunology·D HourcadeJ P Atkinson
Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·T Kristensen, B F Tack
Jan 15, 1988·The Biochemical Journal·J RipocheR B Sim
Mar 1, 1980·Analytical Biochemistry·C Labarca, K Paigen
Mar 20, 1997·Biochimica Et Biophysica Acta·E RothermelJ Zwirner
Feb 19, 2002·Laboratory Investigation; a Journal of Technical Methods and Pathology·Gerald SchlafOtto Götze

❮ Previous
Next ❯

Citations

Jul 18, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ravi MaruvadaC E Rubens
Feb 1, 2013·Shock·Silvia M UriarteKenneth R McLeish
May 1, 2007·Current Opinion in Genetics & Development·Andrew DeWanJosephine Hoh
Oct 31, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Molly S BolgerJo Rae Wright
Apr 5, 2020·International Journal of Molecular Sciences·Andrés D KleinSilvana Zanlungo
Jul 11, 2007·Shock·Michael A FlierlMarkus S Huber-Lang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.