Impairment of Survival Signaling and Efferocytosis In Trpc3-Deficient Macrophages

Publication year: 2011
Source: Biochemical and Biophysical Research Communications, In Press, Accepted Manuscript, Available online 13 June 2011

Jean-Yves, Tano , Kathryn, Smedlund , Robert, Lee , Joel, Abramowitz , Lutz, Birnbaumer , …

We have recently shown that in macrophages proper operation of the survival pathways phosphatidylinositol-3-kinase (PI3K)/AKT and Nuclear Factor kappa B (NFkB) has an obligatory requirement for constitutive, non-regulated Ca2+ influx. In the present work we examined if Transient Receptor Potential Canonical 3 (TRPC3), a member of the TRPC family of Ca2+-permeable cation channels, contributes to the constitutive Ca2+ influx that supports macrophage survival. We used bone marrow-derived macrophages obtained from TRPC3-/- mice to determine the activation status of survival signaling pathways, apoptosis and their efferocytic properties. Treatment of TRPC3+/+ macrophages with the pro-apoptotic cytokine TNFα induced time-dependent phosphorylation of IκBα,…

 Highlights: ► We examined the role of TRPC3 channel in macrophage survival, apoptosis and efferocytic properties. ► TRPC3-deficient macrophages exhibit impaired survival signaling, increased apoptosis and impaired efferocytosis. ► These findings suggest that macrophage TRPC3 is an essential component for macrophage survival and clearance of apoptotic cells.