TRPV2 has a pivotal role in macrophage particle binding and phagocytosis.
Macrophage phagocytosis is critical for defense against pathogens. Whereas many steps of phagocytosis involve ionic flux, the underlying ion channels remain ill defined. Here we show that zymosan-, immunoglobulin G (IgG)- and complement-mediated particle binding and phagocytosis were impaired in macrophages lacking the cation channel TRPV2. TRPV2 was recruited to the nascent phagosome and depolarized the plasma membrane. Depolarization increased the synthesis of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)), which triggered the partial actin depolymerization necessary for occupancy-elicited phagocytic receptor clustering. TRPV2-deficient macrophages were also defective in chemoattractant-elicited motility. Consequently, TRPV2-deficient mice showed accelerated mortality and greater organ bacterial load when challenged with Listeria monocytogenes. Our data demonstrate the participation of TRPV2 in early phagocytosis and its fundamental importance in innate immunity.
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Tiffany M
TM
Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Park
Una
U
Vonakis
Becky M
BM
Raben
Daniel M
DM
Soloski
Mark J
MJ
Caterina
Michael J
MJ
D000199:Actins / Q000276:immunology; D000818:Animals; D002118:Calcium / Q000276:immunology; D015220:Calcium Channels / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D017452:Receptors, IgG / Q000276:immunology; D012430:Ruthenium Red / Q000494:pharmacology; D016019:Survival Analysis; D050916:TRPV Cation Channels / Q000276:immunology*
D000199:Actins; D015220:Calcium Channels; C485701:Fcgr1 protein, mouse; D034741:RNA, Small Interfering; D017452:Receptors, IgG; D050916:TRPV Cation Channels; C485717:Trpv2 protein, mouse; D012430:Ruthenium Red; D002118:Calcium