title: Phospholipase D1 regulates phagocyte adhesion.
abstract: Adhesion is a fundamental cellular response that is essential to the physiologic processes of development, differentiation, proliferation, and motility, as well as to the pathology of inflammation, transformation, and metastasis. Adhesion of phagocytic leukocytes is a critical modulator of antimicrobial and cytotoxic functions, including the respiratory burst, secretion, and apoptosis. Because phospholipase D (PLD) is linked to several signaling pathways implicated in these processes, we tested the hypothesis that PLD regulates phagocyte adhesion. Adhesion of primary human neutrophils and monocyte-derived macrophages to fibronectin was accompanied by marked stimulation of PLD activity. Similarly, adhesion of both human (PLB, THP-1) and murine (RAW) myeloid-macrophage cell lines to fibronectin, fibrinogen, collagen, or plastic resulted in significant activation of PLD. Stimulation of PLD activity was rapid and persisted for at least 90 min. Confocal microscopy indicated that PLD1 exhibited partial colocalization with actin filaments at the adherent interface, in proximity to the focal adhesion protein, paxillin. Reductions in PLD activity by chemical inhibitors or specific short-interfering RNA-induced knockdown of PLD1 resulted in significant inhibition of phagocyte adhesion and was accompanied by reductions in total cellular F-actin. These data support the hypotheses that adhesion stimulates PLD activity, and that PLD1 regulates the initial stages of phagocyte adhesion. Stimulation of PLD activity may promote adhesion-dependent phagocyte effector responses.
authors.affiliation: Inflammation Program, Division of Infectious Diseases, Department of Internal Medicine, University of Iowa Carver College of Medicine, 2501 Crosspark Road, Iowa City, IA 52242, USA.
authors.forename: Shankar S
authors.initials: SS
authors.lastname: Iyer
authors.forename: Reitu S
authors.initials: RS
authors.lastname: Agrawal
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Thompson
authors.forename: Steven
authors.initials: S
authors.lastname: Thompson
authors.forename: James A
authors.initials: JA
authors.lastname: Barton
authors.forename: David J
authors.initials: DJ
authors.lastname: Kusner
mesh_terms: D000199:Actins / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology; D022423:Myeloid Cells / Q000166:cytology / Q000201:enzymology; D010586:Phagocytes / Q000166:cytology* / Q000201:enzymology*; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D000199:Actins; D018821:CD18 Antigens; D010739:Phospholipase D; C106801:phospholipase D1