M1 Macrophages Are More Susceptible to Necroptosis.

Macrophages play a crucial role in host innate immune defense against infection and tissue injury. Although macrophage activation and polarization has been well studied, we know less regarding the role of macrophage activation/polarization in inflammation-associated necrotic cell death. By using bone marrow-derived macrophages, we have recently demonstrated that M1 macrophages are much more susceptible than M0 and M2 subtypes of macrophages to necrotic cell death. Moreover, we showed that the enhanced necroptosis in M1 macrophages is dependent on the kinase activity of receptor-interacting protein kinase-3 (RIPK3) and may involve the upregulation of key necroptosis signaling molecules including RIPK3, mixed lineage kinase domain-like protein, and Z-DNA/ RNA binding protein 1. Our findings provide novel insights into the mechanisms of M1 macrophage engagement in inflammation and tissue injury.