Enhancement of complement-mediated prostaglandin synthesis and bone resorption by arachidonic acid and inhibition by cortisol.

ABSTRACT

Arachidonic acid enhances the resorption of fetal rat long bones cultured in the presence of complement and antibodies reactive with rat cell surface antigens as determined by the release of previously incorporated 45Ca by the bones. This effect is attributed to enhanced complement-mediated synthesis of PGE2 by the bones since the levels of PGE2 detectable by radioimmunoassay were greater in cultures containing arachidonic acid, complement and antibody than in those containing only complement and antibody. In addition indomethacin, RO 20-5720 and cortisol inhibited the arachidonic acid induced elevation of PGE2 and 45Ca levels in the supernatants of bones cultured in the presence of complement and antibody. The stimulatory activity of arachidonic acid was not observed if complement was destroyed by heating or if C6 deficient serum was utilized. However, arachidonic acid was effective in cultures containing C6 deficient serum supplemented with functionally purified C6, demonstrating a requirement for late complement components. The increased membrane phospholipid turnover known to be initiated by complement activation is apparently a prerequisite for stimulation of prostaglandin synthesis and resultant bone resorption by arachidonic acid.