PMID: 2511764Nov 1, 1989Paper

Complement C5b-9 complex activates phospholipases in glomerular epithelial cells

The American Journal of Physiology
A V CybulskyJ V Bonventre

Abstract

In rat membranous nephropathy, formation of the C5b-9 membrane attack complex (MAC) leads to proteinuria in association with glomerular visceral epithelial cell (GEC) injury. These alterations in GEC function and morphology might result from changes in intracellular free Ca2+ concentration [( Ca2+]i) and activation of phospholipases. We demonstrate that in cultured rat GEC, antibody-directed formation of noncytolytic amounts of the MAC induced a rapid and sustained increase in [Ca2+]i that was partly inhibited by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The MAC elevated levels of inositol bis- (IP2) and trisphosphate (IP3), as well as 1,2-diacylglycerol (DAG) and phosphatidic acid (PA). In permeabilized GEC, IP3 released Ca2+ from intracellular stores. Cellular 45Ca2+ uptake was also increased by the MAC. Thus, in GEC, the MAC induced Ca2+ mobilization from intracellular stores secondary to activation of phospholipase C and production of IP3, as well as enhanced Ca2+ influx. In addition, C5b-9 stimulated release of arachidonic acid (AA), prostaglandin F2 alpha, and thromboxane A2. Indomethacin partially inhibited the increase in DAG levels observed with the MAC, whereas the prostaglandin H2/...Continue Reading

Citations

Sep 15, 2005·American Journal of Physiology. Renal Physiology·Andrey V CybulskyDavid J Salant
Feb 9, 2000·American Journal of Physiology. Renal Physiology·H Pavenstädt
May 12, 2000·American Journal of Physiology. Renal Physiology·J HughesR J Johnson
Feb 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Feng LinM Edward Medof
Jan 4, 2008·American Journal of Physiology. Renal Physiology·Daniel CohenTomoko Takano
Dec 3, 2003·American Journal of Physiology. Renal Physiology·Andrey V CybulskyLudmilla Le Berre
Mar 26, 2002·Journal of the American Society of Nephrology : JASN·Huaiping YuanDavid J Salant

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