title: Synergy between extracellular group IIA phospholipase A2 and phagocyte NADPH oxidase in digestion of phospholipids of Staphylococcus aureus ingested by human neutrophils.
abstract: Acute inflammatory responses to invading bacteria such as Staphylococcus aureus include mobilization of polymorphonuclear leukocytes (PMN) and extracellular group IIA phospholipase A2 (gIIA-PLA2). Although accumulating coincidentally, the in vitro anti-staphylococcal activities of PMN and gIIA-PLA2 have thus far been studied separately. We now show that degradation of S. aureus phospholipids during and after phagocytosis by human PMN requires the presence of extracellular gIIA-PLA2. The concentration of extracellular gIIA-PLA2 required to produce bacterial digestion was reduced 10-fold by PMN. The effects of added gIIA-PLA2 were greater when present before phagocytosis but even apparent when added after S. aureus were ingested by PMN. Related group V and X PLA2, which are present within PMN granules, do not contribute to bacterial phospholipid degradation during and after phagocytosis even when added at concentrations 30-fold higher than that needed for action of the gIIA-PLA2. The action of added gIIA-PLA2 required catalytically active gIIA-PLA2 and, in PMN, a functional NADPH oxidase but not myeloperoxidase. These findings reveal a novel collaboration between cellular oxygen-dependent and extracellular oxygen-independent host defense systems that may be important in the ultimate resolution of S. aureus infections.
authors.affiliation: The Inflammation Program, University of Iowa and Veterans Affairs Medical Center, Iowa City 52242, USA.
authors.forename: Jon K
authors.initials: JK
authors.lastname: Femling
authors.forename: William M
authors.initials: WM
authors.lastname: Nauseef
authors.forename: Jerrold P
authors.initials: JP
authors.lastname: Weiss
mesh_terms: D002308:Cardiolipins / Q000378:metabolism; D004357:Drug Synergism; D054501:Group II Phospholipases A2; D054505:Group V Phospholipases A2; D054509:Group X Phospholipases A2; D006801:Humans; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D019255:NADPH Oxidases / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology* / Q000382:microbiology / Q000648:ultrastructure; D010100:Oxygen / Q000378:metabolism; D009195:Peroxidase / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D010715:Phosphatidylglycerols / Q000378:metabolism; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: D002308:Cardiolipins; D010715:Phosphatidylglycerols; D010743:Phospholipids; D009195:Peroxidase; D019255:NADPH Oxidases; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054505:Group V Phospholipases A2; D054509:Group X Phospholipases A2; C516365:PLA2G10 protein, human; D054467:Phospholipases A2; C101424:phospholipase A2-V, Trimeresurus; D010100:Oxygen