Extracellular ATP and P2 receptors are required for IL-8 to induce neutrophil migration.
The chemokine interleukin 8 (IL-8) is a major chemoattractant for human neutrophils. Here, we demonstrate novel evidence that IL-8-induced neutrophil chemotaxis requires a concurrent activation of P2 receptors, most likely the P2Y(2) which is dominantly expressed in these cells. Indeed, the migration of human neutrophils towards IL-8 was significantly inhibited by the P2Y receptor antagonists, suramin and reactive blue 2 (RB-2) and potentiated by a P2Y(2) ligand, ATP, but insensitive to specific antagonists of P2Y(1), P2Y(6) and P2Y(11) receptors. Adenosine had no effect on neutrophil migration towards IL-8 which contrasted with the stimulatory effect of this molecule on neutrophil chemotaxis caused by formyl-Met-Leu-Phe (fMLP or fMLF). Taken together, these data suggest that extracellular ATP is necessary for IL-8 to exert its chemotactic effect on neutrophils.
Kukulski
Filip
F
Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Université Laval, 2705, Boulevard Laurier, Local T1-49, Que., Canada G1V 4G2.
Ben Yebdri
Fethia
F
Lecka
Joanna
J
Kauffenstein
Gilles
G
Lévesque
Sébastien A
SA
Martín-Satué
Mireia
M
Sévigny
Jean
J
D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D002630:Chemotactic Factors / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D045604:Extracellular Fluid / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D020033:Protein Isoforms / Q000276:immunology; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013498:Suramin / Q000378:metabolism
D002630:Chemotactic Factors; D016209:Interleukin-8; D020033:Protein Isoforms; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D013498:Suramin; D000255:Adenosine Triphosphate; D000241:Adenosine