Stem cell factor protects bone marrow-derived cultured mast cells (BMCMC) from cytocidal effect of nitric oxide secrected by fibroblasts in murine BMCMC-fibroblasts coculture

The survival of mast cells are dependent on two kinds of growth factors, one derived from T cells (IL-3) and another derived from fibroblasts (stem cell factor [SCF]). The 3T3 fibroblast cell line derived from WCB6F₁-+/+ mouse embryos (+/+ 3T3 fibroblasts) supported the proliferation of bone marrow-derived cultured mast cells (BMCMC) in the PWM stimulated spleen cell conditioned medium (PWM-SCM), whereas the 3T3 fibroblast cell line from WCB6F₁-Sl/Sl(d) mouse embryos (Sl/Sl(d) 3T3 fibroblasts) did not. To study the role of nitric oxide (NO) on the growth of mast cells in BMCMC-fibroblasts coculture, we used a NO synthase inhibitor, N(G)-monomethyl-L-arginine (N(G)MMA). N(G)MMA recovered survival and maintained proliferation of mast cells in BMCMC-Sl/Sl(d) 3T3 fibroblasts coculture. Sl/Sl(d) 3T3 fibroblasts as well as 3T3 fibroblasts from NIH-+/+, BALB-+/+ or Swiss-+/+ mouse embryos secreted NO in PWM-SCM, but not in α-MEM. SCF protected BMCMC from cytotoxicity of exogenous NO in IL-3-supplemented α-MEM. We concluded that SCF might protect BMCMC from cytocidal effect of NO in BMCMC-fibroblasts coculture.