RAT KUPFFER CELL-DERIVED NITRIC-OXIDE MODULATES INDUCTION OF LYMPHOKINE-ACTIVATED KILLER-CELL

Background & Aims: Nitric oxide is now recognized to regulate immune r esponses and cell viability in various organs. The present study was d esigned to clarify whether NO released from Kupffer cells modulates th e lymphokine-activated killer (LAK) activity of interleukin 2 (IL-2)-t reated splenocytes. Methods: Splenocytes and Kupffer cells were isolat ed from male Wistar rats and cocultured for 48 hours in the presence o f lipopolysaccharide (1 mu g/mL). The splenocyte LAK activity and expr ession of IL-2 receptor were determined. Results: Kupffer cells with l ipopolysaccharide reduced the IL-2 receptor expression and LAK activit y of splenocytes. The addition of either N-G-monomethyl-L-arginine, an inhibitor of NO synthesis, or aminoguanidine, an inhibitor of inducib le NO synthase, to the medium reversed the suppression of IL-2 recepto r expression and LAK activity by lipopolysaccharide-stimulated Kupffer cells. 8-bromoguanosine 3',5'-cyclic monophosphate and NO donors decr eased the splenocyte LAK activity and IL-2 receptor expression. Treatm ent with lipopolysaccharide increased the inducible NO synthase activi ty as well as the nitrite and nitrate levels in the culture medium of Kupffer cells but not in splenocytes. Conclusions: The results of this study suggest that NO produced by the inducible NO synthase of Kupffe r cells in response to lipopolysaccharide modulates the IL-2 receptor expression and LAK activity of splenocytes.