LACK OF INVOLVEMENT OF NITRIC-OXIDE IN THE MACROPHAGE-MEDIATED INHIBITION OF SPLEEN-CELL PROLIFERATION DURING EXPERIMENTAL CRYPTOCOCCOSIS

We investigated the proliferative response to mitogens of spleen monon uclear (Spm) cells from Cryptococcus neoformans-infected rats. We dete rmined reactive oxygen intermediates (ROI) and nitric oxide (NO) produ ction by peritoneal and Spm cells, and evaluated the correlation of th e proliferative response with NO and ROI production. The proliferative response of Spm cells from infected rats dramatically decreased at 14 and 21 days postinfection (PI). The unresponsiveness of Spm cells fro m 14-day infected rats was not abrogated by the addition of L-NAME and AG, indicating that NO is not involved in the antiproliferative respo nse of experimental cells. When SOD, catalase, and indomethacin were a dded to the cultures, the suppression was still observed, indicating t hat ROI and prostaglandins are not involved in the unresponsiveness of lymphocytes. The proliferative response of lymphocytes from 14-day in fected rats was significantly improved when cultures were made in the presence of Con A and exogenous IL-2. Additionally, a purified T-rich fraction from infected rats cultured with control macrophages recovere d the normal proliferative response. This result-indicates that macrop hages from infected rats mediate the unresponsiveness of lymphocytes, probably by reducing the ability of lymphocytes to secrete IL-2. (C) 1 998 Academic Press.