Phospholipase A2 as leukotriene B4 secretagogue for human polymorphonuclear leukocytes.
High levels of soluble phospholipase A2 (PLA2) activity have been detected in tissues fluids associated with inflammatory diseases. However, the cellular origin for PLA2 has not been demonstrated. Several groups of investigators have proposed that platelets, macrophages and chondrocytes may be the cellular source of this enzyme. In fact, soluble PLA2 is secreted extracellularly from rabbit and rat chondrocytes and from human synovial cells in response to cytokine stimulation (1). PLA2 activity has been shown to be increased upon stimulation by the chemotactic peptide (f-met-leu-phe) and thrombin in neutrophils and platelets (2). PLA2 has been found to have pro-inflammatory effects and causes a dose dependent infiltration of leukocytes and increased vascular permeability (3). The vascular actions of PLA2 have been proposed to be mediated through the release of prostaglandin E2 and thromboxane (4). We have reported that purified PLA2 from snake venom stimulated the release of leukotrienes and lipoxins from endogenous sources in porcine leukocytes. However, there is no information regarding the mechanism of action of human PLA2 on inflammatory cells and the generation of leukotrienes. In this report, we present evidence that PLA2 isolated from human platelets can stimulate the production of leukotriene B4 from human polymorphonuclear leukocytes. These results suggest that soluble PLA2 may function as a secretagogue of LTB4 in inflammatory sites and further amplify the inflammatory processes by inducing chemotaxis of circulating leukocytes.
Lam
B K
BK
Department of Physiology, New York Medical College, Valhalla.
Yang
C Y
CY
Wong
P Y
PY
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007975:Leukotriene B4 / Q000097:blood* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000097:blood / Q000494:pharmacology*; D054467:Phospholipases A2; D013056:Spectrophotometry, Ultraviolet
D001095:Arachidonic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2