Dendritic-cell activation by secretory phospholipase A2.
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.
Ramoner
Reinhold
R
Department of Urology and Kompetenzzentrum Medizin Tirol (KMT), Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Putz
Thomas
T
Gander
Hubert
H
Rahm
Andrea
A
Bartsch
Georg
G
Schaber
Claudia
C
Thurnher
Martin
M
D000818:Animals; D000954:Antigens, Surface; D001514:Bee Venoms / Q000201:enzymology; D001516:Bees; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007109:Immunity; D007375:Interleukin-1 / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism / Q000494:pharmacology*; D054467:Phospholipases A2; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D000954:Antigens, Surface; D001514:Bee Venoms; D005227:Fatty Acids; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054467:Phospholipases A2