Induction of suppression by a murine nonspecific suppressor-inducer cell line (M1-A5). II. The role of prostaglandins.

A murine nonspecific suppressor-inducer cell line (M1-A5) was generated from the spleen cells of a mouse bearing an advanced methylcholanthrene-induced fibrosarcoma. We previously demonstrated the capability of M1-A5 cells to activate suppressor cells from the spleen cells of unprimed mice. We demonstrate here that induction of suppression by M1-A5 cells was blocked by acetylsalicylic acid (ASA) and ibuprofen at concentrations which block prostaglandin (PG) synthesis. Maximal blockade of the induction of suppression by M1-A5 cells was seen when ASA was added at the initiation of culture, and it required inhibition of PG synthesis at the level of the inducer (M1-A5 cells) population. However, ASA blockade of suppressor cell activation by M1-A5 cells was not due to ASA acetylating suppressor-inducing factor. Exogenously added PGE1, PGE2, and PGI2, but not PGF2 alpha or PGD2, were able to restore the inducing capability of M1-A5 cells, which had been blocked by ASA. However, PGE1, PGE2, or PGI2 did not reconstitute an inactive suppressor-inducing factor. These results suggest that PG act to modulate the release of suppressor-inducing factor from M1-A5 cells.