A novel receptor cross-talk between the ATP receptor P2Y2 and formyl peptide receptors reactivates desensitized neutrophils to produce superoxide.
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 (P2Y2) 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., P2Y2 ligation reactivated FPR, but not vice versa and was sensitive to the phosphatase inhibitor calyculinA. Further, we show that the cross talk between P2Y2 and FPR bypassed cytosolic Ca(2+) 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.
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Göteborg 413 46, Sweden.
Karin
K
Önnheim
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Göteborg 413 46, Sweden.
Karin
K
Christenson
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Göteborg 413 46, Sweden.
Michael
M
Gabl
PharmaCenter Bonn, Pharmaceutical Chemistry I at the Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Joachim C
JC
Burbiel
PharmaCenter Bonn, Pharmaceutical Chemistry I at the Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Christa E
CE
Müller
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Göteborg 413 46, Sweden; Division of Biocomputing, Department of Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Tudor I
TI
Oprea
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Göteborg 413 46, Sweden.
Johan
J
Bylund
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Göteborg 413 46, Sweden.
Claes
C
Dahlgren
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Göteborg 413 46, Sweden. Electronic address: Huamei.forsman@rheuma.gu.se.
Huamei
H
Forsman
D008841:Actin Cytoskeleton; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008387:Marine Toxins; D019255:NADPH Oxidases / Q000378:metabolism; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; C469986:FPR1 protein, human; D008387:Marine Toxins; D010080:Oxazoles; D058921:Purinergic P2Y Receptor Antagonists; D044042:Receptors, Formyl Peptide; D058473:Receptors, Purinergic P2Y2; D053778:Thiazolidines; D013481:Superoxides; D013498:Suramin; C059041:calyculin A; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D019255:NADPH Oxidases; D010749:Phosphoprotein Phosphatases; C050025:cyclosporin H; C037067:latrunculin A; D002118:Calcium
ATP; Cross-talk; Formyl peptides; G-protein coupled receptors; Neutrophils