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Journal of Lipid Research, Vol. 50, S231-S236, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Signaling

Signal-activated phospholipase regulation of leukocyte chemotaxis

Martha K. Cathcart¹

Departments of Cell Biology and Molecular Medicine, Lerner Research Institute and Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195

This work was supported by National Institutes of Health Grants HL-61971 and HL-74451 and by the National Center for Research Resources (CTSA 1UL1RR024989), Cleveland, OH.

Published, JLR Papers in Press, Janury 2, 2009.

¹ To whom correspondence should be addressed. e-mail: cathcam{at}ccf.org

ABSTRACT

Signal-activated phospholipases are a recent focus of the rapidly growing field of lipid signaling. The extent of their impact on the pathways regulating diverse cell functions is beginning to be appreciated. A critical step in inflammation is the attraction of leukocytes to injured or diseased tissue. Chemotaxis of leukocytes, a requisite process for monocyte and neutrophil extravasation from the blood into tissues, is a critical step for initiating and maintaining inflammation in both acute and chronic settings. Recent studies have identified new important and required roles for two signal-activated phospholipases A₂ (PLA₂) in regulating chemotaxis. The two intracellular phospholipases, cPLA₂ (Group IVA) and iPLA₂β (Group VIA), act in parallel to provide distinct lipid mediators at different intracellular sites that are both required for leukocytes to migrate toward the chemokine monocyte chemoattractant protein-1. This review will summarize the separate roles of these phospholipases as well as what is currently known about the influence of two other classes of intracellular signal-activated phospholipases, phospholipase C and phospholipase D, in regulating chemotaxis in eukaryotic cells, but particularly in human monocytes. The contributions of these phospholipases to chemotaxis both in vitro and in vivo will be highlighted.

Supplementary key words chronic inflammation • macrophage • lipid mediators • monocyte

Abbreviations: AA, arachidonic acid; Cox, cyclooxygenase; cPLA₂, cytosolic phospholipase A₂; Cyp, cytochrome p450 epoxygenase; EET, epoxyeicosatrienoic acids; iPLA₂, calcium-independent phospholipase A₂; LO, lipoxygenase; LPA, lysophosphatidic acid; MCP-1, monocyte chemoattractant protein-1; PA, phosphatidic acid; PLA₂, phospholipase A₂; PLC, phospholipase C; PLD, phospholipase D; PPAR, peroxisome proliferator-activated receptor

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