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Published online before print November 7, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0405226

Received for publication April 25, 2005.
Revised September 28, 2005.
Accepted for publication October 3, 2005.

Article

Prostaglandin E₂ promotes degranulation-independent release of MCP-1 from mast cells

Takayuki Nakayama ^*@, Noriko Mutsuga , Lei Yao ^*, and Giovanna Tosato ^*

*Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, and Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland

^@ To whom correspondence should be addressed. E-mail: Nakayamt{at}mail.nih.gov.

	Abstract

Mast cells (MCs) are common components of inflammatory infiltrates and a source of proangiogenic factors. Inflammation is often accompanied by vascular changes. However, little is known about modulation of MC-derived proangiogenic factors during inflammation. In this study, we evaluated the effects of the proinflammatory mediator prostaglandin E₂ (PGE₂) on MC expression and release of proangiogenic factors. We report that PGE₂ dose-dependently induces primary MCs to release the proangiogenic chemokine monocyte chemoattractant protein-1 (MCP-1). This release of MCP-1 is complete by 2 h after PGE₂ exposure, reaches levels of MCP-1 at least 15-fold higher than background, and is not accompanied by degranulation or increased MCP-1 gene expression. By immunoelectron microscopy, MCP-1 is detected within MCs at a cytoplasmic location distinct from the secretory granules. Dexamethasone and cyclosporine A inhibit PGE₂-induced MCP-1 secretion by 60%. Agonists of PGE₂ receptor subtypes revealed that the EP₁ and EP₃ receptors can independently mediate MCP-1 release from MCs. These observations identify PGE₂-induced MCP-1 release from MCs as a pathway underlying inflammation-associated angiogenesis and extend current understanding of the activities of PGE₂.

Key Words: inflammation • chemokine • angiogenesis

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