The role of calcium signaling in phagocytosis.
Immune cells kill microbes by engulfing them in a membrane-enclosed compartment, the phagosome. Phagocytosis is initiated when foreign particles bind to receptors on the membrane of phagocytes. The best-studied phagocytic receptors, those for Igs (FcgammaR) and for complement proteins (CR), activate PLC and PLD, resulting in the intracellular production of the Ca(2+)-mobilizing second messengers InsP3 and S1P, respectively. The ensuing release of Ca(2+) from the ER activates SOCE channels in the plasma and/or phagosomal membrane, leading to sustained or oscillatory elevations in cytosolic Ca(2+) concentration. Cytosolic Ca(2+) elevations are required for efficient ingestion of foreign particles by some, but not all, phagocytic receptors and stringently control the subsequent steps involved in the maturation of phagosomes. Ca(2+) is required for the solubilization of the actin meshwork that surrounds nascent phagosomes, for the fusion of phagosomes with granules containing lytic enzymes, and for the assembly and activation of the superoxide-generating NADPH oxidase complex. Furthermore, Ca(2+) entry only occurs at physiological voltages and therefore, requires the activity of proton channels that counteract the depolarizing action of the phagocytic oxidase. The molecules that mediate Ca(2+) ion flux across the phagosomal membrane are still unknown but likely include the ubiquitous SOCE channels and possibly other types of Ca(2+) channels such as LGCC and VGCC. Understanding the molecular basis of the Ca(2+) signals that control phagocytosis might provide new, therapeutic tools against pathogens that subvert phagocytic killing.
Nunes
Paula
P
Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
Demaurex
Nicolas
N
D000818:Animals; D020013:Calcium Signaling; D006801:Humans; D010587:Phagocytosis; D010588:Phagosomes / Q000502:physiology; D020239:Receptor Cross-Talk; D011951:Receptors, Complement / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology
D011951:Receptors, Complement; D017452:Receptors, IgG