A novel receptor cross-talk between the ATP receptor P2Y(2) and formyl peptide receptors reactivates desensitized neutrophils to produce superoxide

作者:Onnheim Karin; Christenson Karin; Gabl Michael; Burbiel Joachim C; Mueller Christa E; Oprea Tudor L; Bylund Johan; Dahlgren Claes; Forsman Huamei*
来源:Experimental Cell Research, 2014, 323(1): 209-217.
DOI:10.1016/j.yexcr.2014.01.023

摘要

Neutrophils express several G-protein coupled receptors (GPCRs) and they cross regulate each other. We described a novel cross-talk mechanism in neutrophils, by which signals generated by the receptor for ATP (P2Y(2)) reactivate desensitized formyl peptide receptors (FPRs) so that these ligand-bound inactive FPRs resume signaling. At the signaling level, the cross-talk was unidirectional, i.e., P2Y(2) ligation reactivated FPR, but not vice versa and was sensitive to the phosphatase inhibitor calyculinA. Further, we show that the cross talk between P2Y(2) and FPR bypassed cytosolic Ca2+ transients and did not rely on the actin cytoskeleton. In summary, our data demonstrate a novel cross-talk mechanism that results in reactivation of desensitized FPRs and, an amplification of the neutrophil response to ATP.

  • 出版日期2014-4-15