Phospholipases and phagocytosis: the role of phospholipid-derived second messengers in phagocytosis

Phagocytosis, the process by which leukocytes recognize and destroy invadin g pathogens, is essential for host defense. The binding of foreign organism s to phagocytic leukocytes initiates a complex signaling cascade which ulti mately results in the entrapment and destruction of the pathogen, The signa l transduction pathway mediating phagocytosis is the subject of intense inv estigation and is known to include protein tyrosine kinases, GTP-binding pr oteins, protein kinase C (PKC), actin polymerization and membrane movement. A rapidly expanding body of evidence suggests that phospholipases play an integral role in phagocytosis by generating essential second messengers. He re we review the data linking activation of phospholipase A(2) (PLA(2)), ph ospholipase C (PLC), phospholipase D (PLD), and phosphoinositide 3-OH kinas e (PI(3)K) to antibody (IgG)-mediated phagocytosis. Evidence is presented t hat (1) PLA(2)-derived arachidonic acid (AA) stimulates NADPH oxidase and m embrane redistribution during phagocytosis, (2) the inositol-3,4,5-triphosp hale (IP3) and diacylglycerol (DAG) products of PLC activate NADPH oxidase and PKC, and (3) sequential activation of PLD and phosphatidic acid phospho hydrolase may provide an alternative pathway for generation of DAG. Additio nally, considerable evidence exists that wortmannin, a P1(3)K inhibitor, de presses phagocytosis. This finding is discussed in the context of the exten sive effects PI(3)K products have on endocytosis and exocytosis and the pot ential role of membrane redistribution in phagocytosis. Finally, a model is presented which integrates data obtained from a variety of phagocytic syst ems and illustrates potential interactions that may exist between phospholi pase-derived second messengers and signaling events required for phagocytos is. (C) 1999 Elsevier Science Ltd. All rights reserved.