The Role of CD38 in Fc gamma receptor (FcγR)-mediated Phagocytosis in Murine Macrophages

Phagocytosis is a crucial event in the immune system that allows cells to engulf and eliminate pathogens. This is mediated through the action of immunoglobulin (IgG)opsonized microbes acting on Fcγ receptors (FcγR) on macrophages, which results in sustained levels of intracellular Ca through the mobilization of Ca second messengers. It is known that the ADP-ribosyl cyclase is responsible for the rise in Ca levels after FcγR activation. However, it is unclear whether and how CD38 is involved in FcγRmediated phagocytosis. Here we show that CD38 is recruited to the forming phagosomes during phagocytosis of IgG-opsonized particles and produces cyclic-ADP-ribose which acts on ER Ca stores, thus allowing an increase in FcγR activation-mediated phagocytosis. Ca data shows that pretreatment of J774A.1 macrophages with 8-bromo-cADPR, ryanodine, blebbistatin, and various store-operated Ca inhibitors prevented the long lasting Ca signal, which significantly reduced the number of ingested opsonized particles. Ex vivo data with macrophages extracted from CD38 mice also shows a reduced Ca signaling and phagocytic index. Furthermore, a significantly reduced phagocytic index of Mycobacterium bovis BCG was shown in macrophages from CD38 mice in vivo. This http://www.jbc.org/cgi/doi/10.1074/jbc.M111.329003 The latest version is at JBC Papers in Press. Published on March 6, 2012 as Manuscript M111.329003