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

Mast cells (MCs) are common compo- nents of inflammatory infiltrates and a source of proangiogenic factors. Inflammation is often ac- companied by vascular changes. However, little is known about modulation of MC-derived proangio- genic factors during inflammation. In this study, we evaluated the effects of the proinflammatory medi- ator 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 de- granulation or increased MCP-1 gene expression. By immunoelectron microscopy, MCP-1 is de- tected within MCs at a cytoplasmic location distinct from the secretory granules. Dexamethasone and cyclosporine A inhibit PGE2-induced MCP-1 secre- tion by 60%. Agonists of PGE2 receptor sub- types 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 inflam- mation-associated angiogenesis and extend current understanding of the activities of PGE2. J. Leukoc. Biol. 79: 000-000; 2006.