Stimulation of P2 purinergic receptors induces the release of eosinophil cationic protein and interleukin-8 from human eosinophils.
1. Extracellular nucleotides are the focus of increasing attention for their role as extracellular mediators since they are released into the extracellular environment in a regulated manner and/or as a consequence of cell damage. 2. Here, we show that human eosinophils stimulated with different nucleotides release eosinophil cationic protein (ECP) and the chemokine interleukin 8 (IL-8), and that release of these two proteins has a different nucleotide requirement. 3. Release of ECP was triggered in a dose-dependent manner by ATP, UTP and UDP, but not by 2'-&3'-o-(4-benzoyl-benzoyl)adenosine 5'-triphosphate (BzATP), ADP and alpha,beta-methylene adenosine 5' triphosphate (alpha,beta-meATP). Release of IL-8 was triggered by UDP, ATP, alpha,beta-meATP and BzATP, but not by UTP or ADP. Pretreatment with pertussis toxin abrogated nucleotide-stimulated ECP but not IL-8 release. 4. Release of IL-8 stimulated by BzATP was fully blocked by the P2X(7) blocker KN-62, while release triggered by ATP was only partially inhibited. IL-8 secretion due to UDP was fully insensitive to KN-62 inhibition. 5. Priming of eosinophils with GM-CSF increased IL-8 secretion irrespectively of the nucleotide used as a stimulant. 6. It is concluded that extracellular nucleotides trigger secretion of ECP by stimulating a receptor of the P2Y subfamily (possibly P2Y(2)), while, on the contrary, nucleotide-stimulated secretion of IL-8 can be due to activation of both P2Y (P2Y(6)) and P2X (P2X(1) and P2X(7)) receptors.
Idzko
Marco
M
Department of Pneumology, University of Freiburg, D-79104 Freiburg i. Br., Germany. idzko@med1ukl.uni-freiburg.de
Panther
Elisabeth
E
Bremer
Hinrich C
HC
Sorichter
Stephan
S
Luttmann
Werner
W
Virchow
Christian J
CJ
Di Virgilio
Francesco
F
Herouy
Yared
Y
Norgauer
Johannes
J
Ferrari
Davide
D
D001798:Blood Proteins / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000097:blood* / Q000378:metabolism*; D009154:Mutation / Q000187:drug effects*; D009711:Nucleotides / Q000494:pharmacology*; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000235:genetics*; D012260:Ribonucleases / Q000097:blood* / Q000378:metabolism*
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D016209:Interleukin-8; D009711:Nucleotides; D018048:Receptors, Purinergic P2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D012260:Ribonucleases