Rat Kupffer cell-derived nitric oxide modulates induction of lymphokine-activated killer cell.
OBJECTIVE
Nitric oxide is now recognized to regulate immune responses and cell viability in various organs. The present study was designed to clarify whether NO released from Kupffer cells modulates the lymphokine-activated killer (LAK) activity of interleukin 2 (IL-2)-treated splenocytes.


METHODS
Splenocytes and Kupffer cells were isolated from male Wistar rats and cocultured for 48 hours in the presence of lipopolysaccharide (1 microgram/mL). The splenocyte LAK activity and expression of IL-2 receptor were determined.


RESULTS
Kupffer cells with lipopolysaccharide reduced the IL-2 receptor expression and LAK activity of splenocytes. The addition of either NG-monomethyl-L-arginine, an inhibitor of NO synthesis, or aminoguanidine, an inhibitor of inducible NO synthase, to the medium reversed the suppression of IL-2 receptor expression and LAK activity by lipopolysaccharide-stimulated Kupffer cells. 8-bromoguanosine 3',5'-cyclic monophosphate and NO donors decreased the splenocyte LAK activity and IL-2 receptor expression. Treatment with lipopolysaccharide increased the inducible NO synthase activity 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 Kupffer cells in response to lipopolysaccharide modulates the IL-2 receptor expression and LAK activity of splenocytes.
D000704:Analysis of Variance; D000818:Animals; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology* / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism*; D008163:Luminescent Measurements; D008213:Lymphocyte Activation; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D015375:Receptors, Interleukin-2; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase