Abstract
BackgroundThe 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+.ResultsThe 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+.ConclusionsCa2+ 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.
Highlights
The molecular basis for neutrophil recognition of chemotactic peptides is their binding to specific Gprotein-coupled cell surface receptors (GPCRs)
The formylated peptide N-formylmethionyl-leucyl-phenylalanine (fMLF) and WKYMVM peptides activate the NADPHoxidase in neutrophils The NADPH-oxidase activities induced by the FPR1-specific peptide agonist fMLF and the FPR2-specific peptide agonist WKYMVM were of similar magnitude (Fig. 1)
The neutrophil NADPH-oxidase activity was completely inhibited by PBP10 when activation was triggered through FPR2, whereas PBP10 had no inhibitory effect on the FPR1-mediated neutrophil response (Fig 1)
Summary
The molecular basis for neutrophil recognition of chemotactic peptides is their binding to specific Gprotein-coupled cell surface receptors (GPCRs). The molecular basis for cellular recognition of chemoattractants is their binding to specific cell surface receptors [4,5,6,7,8]. The activated receptor initiates a chain of signaling events, starting with dissociation of the receptor-associated G-protein, and subsequently, activation of a number of downstream signaling pathways. In one of these pathways, activation of phosphoinositide-specific phospholipase C (PLC) generates a second messenger following cleavage of PIP2, and this is the starting signal for a transient increase in cytosolic free calcium. Emptying of the storage organelles leads to the entry of extracellular Ca2+ through storeoperated calcium channels in the plasma membrane, thereby prolonging the increase in [Ca2+]i [25,26]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
