EFFECTS OF AN S-ADENOSYL-L-HOMOCYSTEINE HYDROLASE INHIBITOR ON MURINEMACROPHAGE ACTIVATION AND FUNCTION

The S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitor MDL 28,842 has been demonstrated to be a potent inhibitor of T-cel activation, bo th in vitro and in vivo. Although the inhibition of T cells in vitro w as independent of macrophages, the direct effect of MDL 28,842 on macr ophages is unknown. In this report the effects of MDL 28,842 on macrop hage cytokine production, cell-surface antigen expression, and antigen processing and presentation were examined. Lipopolysaccharide (LPS) s timulation of IL-1 synthesis by peritoneal macrophages was not effecte d by MDL 28,842 using cells obtained from B10.A and B10.B mice and wea kly inhibited using cells from BALB/C mice (IC50 > 10 mu M). In contra st, TNF-alpha synthesis by BALB/C macrophages was inhibited by MDL 28, 842 with an IC50 < 0.1 mu M. B1O.A and B10.B macrophages did not produ ce detectable TNF-alpha in response to LPS in this system. Treatment w ith 1-10 mu M MDL 28,842 resulted in a modest decrease in major histoc ompatibility complex class II (MHC-II) determinant expression by Inter feron-gamma-activated macrophages. The expression of other cell-surfac e markers was not altered in the presence of MDL 28,842. The processin g of antigen and its presentation by MHC class-II-positive macrophages to a T-cell hybridoma was also not affected by incubation with MDL 28 ,842.)