Inteferon gamma induces the expression of p21(waf-1) and arrests macrophage cell cycle, preventing induction of apoptosis

Incubation of bone marrow macrophages with lipopolysaccharide (LPS) or inte rferon gamma (IFN gamma) blacks macrophage proliferation. LPS treatment or M-CSF withdrawal arrests the cell cycle at early G(1) and induces apoptosis . Treatment of macrophages with IFN gamma stops the cell cycle later, at th e G(1)/S boundary, induces p21(Waf1), and does not induce apoptosis. Moreov er, pretreatment of macrophages with IFN gamma protects from apoptosis indu ced by several stimuli. Inhibition of p21(Waf1) with antisense oligonucleot ides or using KO mice shows that the induction of p21(Waf1) by IFN gamma me diates this protection. Thus, IFN gamma makes macrophages unresponsive to a poptotic stimuli by inducing p21(Waf1) and arresting the cell cycle at the G(1)/S boundary. Therefore, the cells of the innate immune system could onl y survive while they were functionally active.