title: Peptidoglycan and mannose-based molecular patterns trigger the arachidonic acid cascade in human polymorphonuclear leukocytes.
abstract: The release of arachidonic acid (AA) in response to microorganism-derived products acting on pattern recognition receptors (PRR) was assayed in human polymorphonuclear leukocytes (PMN). Peptidoglycan (PGN) and mannan were found to be strong inducers of AA metabolism, as they produced the release of AA at a similar extent to that produced by agonists of pathophysiological relevance such as complement-coated zymosan particles and IgG immune complexes. In sharp contrast, lipoteichoic acid, LPS, muramyldipeptide, and the bacterial lipoprotein mimic palmitoyl-3-cysteine-serine-lysine-4 failed to do so. Leukotriene B4 and PGE2 were synthesized in response to mannan and PGN, thus suggesting that the lipoxygenase and the cyclooxygenase routes are operative in human PMN in response to pathogen-associated molecular patterns (PAMP). Analysis of the lipid extracts of supernatants and cell pellets as well as pharmacological studies with the calpain inhibitor calpeptin and the cytosolic phospholipase A2 (PLA2) inhibitor pyrrolidine-1 showed the dependence of AA release on cytosolic PLA2-catalyzed reactions. The effect of PGN was not inhibited by previous treatment with anti-TLR2 mAb, thus suggesting a nonarchetypal involvement of the TLR2 signaling route and/or participation of other receptors. Because of the abundance of mannose-based and PGN-containing PAMP in fungi and bacteria and the wide array of PRR in human PMN, these finding disclose a role of prime importance for PAMP and PRR in AA metabolism in the inflammatory response mediated by PMN.
authors.affiliation: Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Cientificas, C/ Sanz y Forés s/n, 47003, Valladolid, Spain.
authors.forename: Isela
authors.initials: I
authors.lastname: Valera
authors.forename: Ana González
authors.initials: AG
authors.lastname: Vigo
authors.forename: Sara
authors.initials: S
authors.lastname: Alonso
authors.forename: Luz
authors.initials: L
authors.lastname: Barbolla
authors.forename: Mariano Sánchez
authors.initials: MS
authors.lastname: Crespo
authors.forename: Nieves
authors.initials: N
authors.lastname: Fernández
mesh_terms: D016824:Antigens, Human Platelet / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D008351:Mannans / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010457:Peptidoglycan / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016824:Antigens, Human Platelet; D008351:Mannans; D010457:Peptidoglycan; D051193:Toll-Like Receptors; C083451:human platelet antigen 1b; D007975:Leukotriene B4; D016718:Arachidonic Acid; D015232:Dinoprostone