PMID- 16275896 OWN - NLM STAT- MEDLINE DCOM- 20060302 LR - 20181203 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 79 IP - 1 DP - 2006 Jan TI - Prostaglandin E2 promotes degranulation-independent release of MCP-1 from mast cells. PG - 95-104 AB - 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 approximately 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. FAU - Nakayama, Takayuki AU - Nakayama T AD - Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. Nakayamt@mail.nih.gov FAU - Mutsuga, Noriko AU - Mutsuga N FAU - Yao, Lei AU - Yao L FAU - Tosato, Giovanna AU - Tosato G LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20051107 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Angiogenesis Inducing Agents) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Immunosuppressive Agents) RN - 0 (Oxytocics) RN - 7S5I7G3JQL (Dexamethasone) RN - 83HN0GTJ6D (Cyclosporine) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Angiogenesis Inducing Agents/immunology/*metabolism MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Cell Degranulation/*drug effects/immunology MH - Cells, Cultured MH - Chemokine CCL2/immunology/*metabolism MH - Cyclosporine/pharmacology MH - Dexamethasone/pharmacology MH - Dinoprostone/immunology/*pharmacology MH - Dose-Response Relationship, Drug MH - Drug Antagonism MH - Immunosuppressive Agents/pharmacology MH - Inflammation/immunology/metabolism/pathology MH - Mast Cells/immunology/*metabolism/ultrastructure MH - Mice MH - Neovascularization, Pathologic/immunology/pathology MH - Oxytocics/immunology/*pharmacology MH - Secretory Vesicles/immunology/metabolism/ultrastructure EDAT- 2005/11/09 09:00 MHDA- 2006/03/03 09:00 CRDT- 2005/11/09 09:00 PHST- 2005/11/09 09:00 [pubmed] PHST- 2006/03/03 09:00 [medline] PHST- 2005/11/09 09:00 [entrez] AID - jlb.0405226 [pii] AID - 10.1189/jlb.0405226 [doi] PST - ppublish SO - J Leukoc Biol. 2006 Jan;79(1):95-104. doi: 10.1189/jlb.0405226. Epub 2005 Nov 7.