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Peptidoglycan and mannose‐based molecular patterns trigger the arachidonic acid cascade in human polymorphonuclear leukocytes
Author(s) -
Valera Isela,
Vigo Ana González,
Alonso Sara,
Barbolla Luz,
Crespo Mariano Sánchez,
Fernández Nieves
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0706451
Subject(s) - lipoteichoic acid , zymosan , peptidoglycan , biology , phospholipase a2 , biochemistry , arachidonic acid , eicosanoid , leukotriene b4 , mannan , mannose , n formylmethionine leucyl phenylalanine , receptor , chemotaxis , inflammation , immunology , enzyme , bacteria , polysaccharide , in vitro , genetics , staphylococcus aureus
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 B 4 and PGE 2 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 A 2 (PLA 2 ) inhibitor pyrrolidine‐1 showed the dependence of AA release on cytosolic PLA 2 ‐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.