First Author | Kang J | Year | 2012 |
Journal | J Biol Chem | Volume | 287 |
Issue | 18 | Pages | 14502-14 |
PubMed ID | 22396532 | Mgi Jnum | J:184883 |
Mgi Id | MGI:5426502 | Doi | 10.1074/jbc.M111.329003 |
Citation | Kang J, et al. (2012) The role of CD38 in Fcgamma receptor (FcgammaR)-mediated phagocytosis in murine macrophages. J Biol Chem 287(18):14502-14 |
abstractText | 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 Fcgamma receptors (FcgammaR) on macrophages, which results in sustained levels of intracellular Ca(2+) through the mobilization of Ca(2+) second messengers. It is known that the ADP-ribosyl cyclase is responsible for the rise in Ca(2+) levels after FcgammaR activation. However, it is unclear whether and how CD38 is involved in FcgammaR-mediated 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(2+) stores, thus allowing an increase in FcgammaR activation-mediated phagocytosis. Ca(2+) data show that pretreatment of J774A.1 macrophages with 8-bromo-cADPR, ryanodine, blebbistatin, and various store-operated Ca(2+) inhibitors prevented the long-lasting Ca(2+) signal, which significantly reduced the number of ingested opsonized particles. Ex vivo data with macrophages extracted from CD38(-/-) mice also shows a reduced Ca(2+) signaling and phagocytic index. Furthermore, a significantly reduced phagocytic index of Mycobacterium bovis BCG was shown in macrophages from CD38(-/-) mice in vivo. This study suggests a crucial role of CD38 in FcgammaR-mediated phagocytosis through its recruitment to the phagosome and mobilization of cADPR-induced intracellular Ca(2+) and store-operated extracellular Ca(2+) influx. |