Nitric oxide promotes growth and major histocompatibility complex-unrestricted cytotoxicity of interleukin-2-activated rat lymphocytes

The effect of nitric oxide (NO) on growth and major histocompatibility comp lex(MHC)-unrestricted cytotoxicity of interleukin(IL)-2-cultivated rat sple en nonadherent mononuclear cells was examined. NO donor sodium nitroprussid e (SNP) at relatively low concentrations increased magnitude, as well as du ration of IL-2-induced proliferative response of nonadherent splenocytes. S NP effect depended completely on released NO, because it was prevented by N O scavenger haemoglobin, but not mimicked by expired SNP solution, unable t o generate NO, or ferricyanide, a second breakdown product of SNP. Other NO donors - SIN-1, SNAP and GSNO failed to exert SNP-like growth-enhancing ac tion, probably as a consequence of rapid NO generation, compared to sustain ed NO release by SNP. All NO-releasing chemicals at high concentration bloc ked IL-2-induced proliferation. Growth-promoting effect of SNP-derived NO w as independent of guanilat cyclase activation, because dibutyryl cGMP did n ot affect IL-2-triggered splenocyte proliferation. Macrophage NO acted in a manner similar to SNP; at low concentrations it promoted IL-2-induced sple nocyte growth, however higher amounts were suppressive. Cytotoxicity of IL- 2-activated splenocytes against NK-sensitive K562 cell line was significant ly increased when SNP was present during cultivation with IL-2. Proportion of NKR-P1(+) and CD25(+) cells, as well as per cell expression of these imp ortant activation molecules were increased upon SNP treatment, suggesting p ossible mechanism for the observed NO action.