Down-regulation of Ia expression on macrophages by sea star factor.

Sea star factor (SSF), a protein of 39,000 Da isolated from the coelomocytes of Asterias forbesi, was found to inhibit the induction of Ia expression on murine macrophages by concanavalin A supernatants. Addition of SSF to cultured macrophages at the same time as the lymphokine preparation significantly reduced the percentage Ia+ cells after 5 days culture, compared to cultures given lymphokine only. Intraperitoneal injection of SSF also reduced the percentage Ia+ peritoneal exudate macrophages by three-fourths in Listeria-infected mice. Addition of the cyclo-oxygenase inhibitor, indomethacin, to macrophage cultures reversed this Ia-suppressive effect of SSF. Since macrophages from endotoxin-unresponsive and endotoxin-responsive mice were both sensitive to the Ia-inhibitory effect of SSF, the induction of arachidonic acid metabolism and the inhibition of Ia appear to be independent of the action of endotoxin. The SSF-induced down regulation of Ia expression may be a major factor in the suppression of primary immune responses to T-dependent antigens previously noted in studies with SSF.