Inteferon γ induces the expression of p21waf-1 and arrests macrophage cell cycle, preventing induction of apoptosis

Incubation of bone marrow macrophages with lipopolysaccharide (LPS) or interferon 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 the G(1)/S boundary, induces p21(Waf1), and does not induce apoptosis. Moreover, pretreatment of macrophages with IFN gamma protects from apoptosis induced by several stimuli. Inhibition of p21(Waf1) with antisense oligonucleotides or using KO mice shows that the induction of p21(Waf1) by IFN gamma mediates this protection. Thus, IFN gamma makes macrophages unresponsive to apoptotic 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 only survive while they were functionally active.