The role of platelet activating factor and other lipid mediators in inflammatory angiogenesis

Jeffrey R. Jackson, Brian Bolognese, Clare A. Mangar, Walter C. Hubbard, Lisa A. Marshall, James D. Winkler

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic inflammatory diseases are often accompanied by intense angiogenesis. A model of inflammatory angiogenesis is the murine air pouch granuloma which has a hyperangiogenic component. Proinflammatory lipid mediator generation is also a hallmark of chronic inflammation and the role of endogenous production of these mediators in angiogenesis is not known. The 14 kDa phospholipase A2 (PLA2) deacylates phospholipid, liberating arachidonic acid, which is used for leukotriene production, and lysophospholipid, which can drive the production of platelet-activating factor (PAF). Therefore, SB 203347, an inhibitor of the 14 kDa PLA2, zileuton, an inhibitor of 5-lipoxygenase, and Ro 24-4736 a PAF receptor antagonist were evaluated for their effects in the murine air pouch granuloma. SB 203347 reduced both LTB4 and PAF, but not PGD2 levels measured in the day 6 granuloma. This correlated with a significant reduction in angiogenesis. Zileuton reduced LTB4 levels as expected, but did not significantly inhibit angiogenesis, whereas Ro 24-4736 potently reduced angiogenesis. These data support the hypothesis that PAF, and to a lesser extent leukotrienes contribute to the angiogenic phenotype in chronic inflammation. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)145-152
Number of pages8
JournalBiochimica et Biophysica Acta - Lipids and Lipid Metabolism
Volume1392
Issue number1
DOIs
StatePublished - May 20 1998

Keywords

  • Angiogenesis
  • Granuloma
  • Leukotriene
  • Phospholipase A
  • Platelet activating factor
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Endocrinology

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