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The Immunostimulatory Peptide WKYMVm‐NH 2 Activates Bone Marrow Mouse Neutrophils via Multiple Signal Transduction Pathways
Author(s) -
Boxio R.,
BossenmeyerPourié C.,
Vanderesse R.,
Dour C.,
Nüße O.
Publication year - 2005
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2005.01651.x
Subject(s) - formyl peptide receptor , microbiology and biotechnology , chemotaxis , signal transduction , wortmannin , biology , receptor , thapsigargin , n formylmethionine leucyl phenylalanine , immunology , intracellular , biochemistry , pi3k/akt/mtor pathway
Abstract G‐protein‐coupled receptors play a major role in the activation of the innate immune system, such as polymorphonuclear neutrophils. Members of the formyl peptide receptor family recognize chemotactic peptides as well the amyloïd‐β peptide and fragments of the human immunodeficiency virus envelope and may thus be implicated in major pathologies. The peptide WKYMVm‐NH 2 probably activates the receptor FPRL1 and its mouse orthologues Fpr‐rs1 and Fpr‐rs2. We examined the stimulation of C57BL6 mouse neutrophils by WKYMVm‐NH 2 and the effects of several inhibitors for intracellular signalling pathways (wortmannin, LY 294002, staurosporin, H‐89, U 73122, thapsigargin and SKF 96365). We show here that WKYMVm‐NH 2 is a powerful stimulator of primary and secondary granule exocytosis as well as superoxide production. The signalling pathway involves phosphoinositide 3‐kinase, protein kinase C, phospholipase C and store‐operated calcium influx. Studies with peptide antagonists suggest that WKYMVm‐NH 2 preferentially activates exocytosis via FPRL1 and not FPR, the major receptor for N‐formylated peptides such as fMLF. However, the signalling pathways activated by WKYMVm‐NH 2 in mouse neutrophils are similar to those activated by fMLF in human neutrophils. Thus, the effect and the signalling pathways of the two agonists and their receptors are at least partially overlapping.