Cyclic AMP as the second messenger for prostaglandin E in modulating suppressor cell-activation by natural suppressor/cytotoxic cells

Abstract

The M1-A5 cell line, isolated from the spleen of a tumor bearing mouse, has been shown to secrete a suppressor cell-inducing factor (SIF) which activates suppressor cells from the spleen cells of unprimed mice. In an earlier publication we demonstrated that prostaglandins of the E series (PGE) regulate the release of SIF from M1-A5 cells. In the present study we provide evidence that cyclic adenosine 3′,5′-monophosphate (cyclic AMP) is the second messenger for PGE in regulating the release of SIF from M1-A5 cells. Our data show that PGE1 and PGE2 stimulate cyclic AMP production by M1-A5 cells. Furthermore, we show that drugs which: (1) elevate cyclic AMP levels (dibutyryl (db) cyclic AMP), (2) inhibit the breakdown of cyclic AMP (theophylline), or (3) stimulate adenylate cyclase (isoproternol and histamine) all restored suppressor cell activation by M1-A5 cells in which PG synthesis had been blocked by acetylsalicylic acid (ASA). Thus, these results are consistent with the hypothesis that cyclic AMP is the second messenger for PGE in modulating the release of SIF from M1-A5 cells.