The FPR2-induced rise in cytosolic calcium in human neutrophils relies on an emptying of intracellular calcium stores and is inhibited by a gelsolin-derived PIP2-binding peptide.
BACKGROUND
The molecular basis for neutrophil recognition of chemotactic peptides is their binding to specific G-protein-coupled cell surface receptors (GPCRs). Human neutrophils express two pattern recognition GPCRs, FPR1 and FPR2, which belong to the family of formyl peptide receptors. The high degree of homology between these two receptors suggests that they share many functional and signal transduction properties, although they exhibit some differences with respect to signaling. The aims of this study were to determine whether FPR2 triggers a unique signal that allows direct influx of extracellular calcium without the emptying of intracellular calcium stores, and whether the gelsolin-derived PIP2-binding peptide, PBP10, selectively inhibits FPR2-mediated transient rise in intracellular Ca2+.


RESULTS
The transient rise in intracellular Ca2+ induced by agonists for FPR1 or FPR2 in human neutrophils occurred also in the presence of a chelator of Ca2+ (EGTA). PBP10 inhibited not only FPR2-induced oxidase activity, but also the transient rise in intracellular Ca2+.


CONCLUSIONS
Ca2+ signaling mediated via FPR2 follows the same route as FPR1, which involves initial emptying of the intracellular stores. PBP10 inhibits selectively the signals generated by FPR2, both with respect to NADPH-oxidase activity and the transient rise in intracellular Ca2+ induced by agonist exposure.
Forsman
Huamei
H
Department of Rheumatology and Inflammation Research, University of Gothenburg, Sweden.
Dahlgren
Claes
C
D064007:Ataxia Telangiectasia Mutated Proteins; D020013:Calcium Signaling / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D018260:Gelsolin / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000094742:Secreted Frizzled-Related Proteins
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004533:Egtazic Acid; D018260:Gelsolin; D008565:Membrane Proteins; D019255:NADPH Oxidases; D010446:Peptide Fragments; D017346:Protein Serine-Threonine Kinases; D043562:Receptors, G-Protein-Coupled; D051192:Receptors, Pattern Recognition; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C527698:gelsolin (160-169); C576597:ATR protein, human