PMID- 15494434 OWN - NLM STAT- MEDLINE DCOM- 20050607 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 105 IP - 9 DP - 2005 May 1 TI - Dendritic-cell activation by secretory phospholipase A2. PG - 3583-7 AB - Dendritic cells (DCs), also referred to as the sentinels of the immune system, induce and coordinate important functions of immune surveillance. DCs acquire immunity-initiating capacity only after a process of maturation usually induced by ligands that bind to members of the tumor necrosis factor (TNF) or toll-like receptor families. Secretory phospholipase A2 (sPLA2), which hydrolyzes the sn-2 ester bond of glycerophospholipids, regulates a variety of cellular functions including migration of endothelial cells and neurite outgrowth. In the present study we investigated the role of sPLA2 in DC biology. We report that human monocyte-derived DC cultures lack sPLA2 activity but respond to exogenous sPLA2. sPLA2 alone and in cooperation with TNF-alpha and interleukin 1 beta (IL-1beta) induced fatty acid release from DC membranes, which was accompanied by upregulation of surface markers and by an increase in the migratory and immunostimulatory capacity of the DCs. Our findings indicate that secreted enzymes such as sPLA2 can contribute to DC maturation and emphasize the role of lipid mediators in the regulation of immune responses. This observation may also have implications for DC-based vaccine development. FAU - Ramoner, Reinhold AU - Ramoner R AD - Department of Urology and Kompetenzzentrum Medizin Tirol (KMT), Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Putz, Thomas AU - Putz T FAU - Gander, Hubert AU - Gander H FAU - Rahm, Andrea AU - Rahm A FAU - Bartsch, Georg AU - Bartsch G FAU - Schaber, Claudia AU - Schaber C FAU - Thurnher, Martin AU - Thurnher M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20041019 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, Surface) RN - 0 (Bee Venoms) RN - 0 (Fatty Acids) RN - 0 (Interleukin-1) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.1.1.32 (Phospholipases A) RN - EC 3.1.1.4 (Phospholipases A2) SB - IM MH - Animals MH - Antigens, Surface MH - Bee Venoms/enzymology MH - Bees MH - Cell Movement MH - Cells, Cultured MH - Dendritic Cells/drug effects/*immunology/metabolism MH - Fatty Acids/metabolism MH - Humans MH - Immunity MH - Interleukin-1/pharmacology MH - Phospholipases A/metabolism/*pharmacology MH - Phospholipases A2 MH - Tumor Necrosis Factor-alpha/pharmacology MH - Up-Regulation EDAT- 2004/10/21 09:00 MHDA- 2005/06/09 09:00 CRDT- 2004/10/21 09:00 PHST- 2004/10/21 09:00 [pubmed] PHST- 2005/06/09 09:00 [medline] PHST- 2004/10/21 09:00 [entrez] AID - S0006-4971(20)45553-3 [pii] AID - 10.1182/blood-2004-08-3001 [doi] PST - ppublish SO - Blood. 2005 May 1;105(9):3583-7. doi: 10.1182/blood-2004-08-3001. Epub 2004 Oct 19.