Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1771, Issue 9, Pages 1235-1245Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2007.06.002
Keywords
inflammation; polymorphonuclear leukocyte; cyclooxygenase; fatty acid; eicosanoids; prostaglandins
Funding
- Canadian Institutes of Health Research [72200, 64315] Funding Source: Medline
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In the present study, we characterized the generation of prostaglandin (PG)E-2 in human neutrophils. We found that the Ca2+-dependent type IV cytosolic phospholipase A(2) (cPLA(2)) was pivotally involved in the COX-2-mediated generation of PGE(2) in response to a calcium ionophore, as determined by the use of selected PLA(2) inhibitors. PGE(2) biosynthesis elicited by bacterial-derived pepticles or by phagocytic stimuli acting on cell surface receptors also showed to be dependent on cPLA2 activity. We then assessed metabolism of unesterified arachidonic acid (AA), and observed that PGE2 production becomes favored over that of LTB4 with higher AA concentrations. Withdrawal of calcium prevented the generation of PGE2 in response to a calcium ionophore but did not affect the up-regulation of COX-2 or its capacity to convert AA, thus limiting its implication at the level of cPLA2 activation. Of the main cicosanoids produced by neutrophils, only LTB4 was able to up-regulate COX-2 expression. Finally, the only PGE synthase isoform found in neutrophils is microsomal PGE synthase-1; it co-localized with COX-2 and its expression appeared mainly constitutive. These results highlight key differences in regulatory processes of the 5-LO and COX pathways, and enhance our knowledge at several levels in the PGE2 biosynthesis in neutrophils. (C) 2007 Elsevier B.V. All rights reserved.
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