Adenosine promotes neutrophil chemotaxis.
We have previously (1-4) demonstrated that adenosine, by engaging specific receptors on the surface of neutrophils, inhibits generation of toxic oxygen metabolites by activated neutrophils and prevents these activated neutrophils from injuring endothelial cells. We now report the surprising observation that engagement of these same neutrophil adenosine receptors promotes chemotaxis to C5 fragments (as zymosan-activated plasma [ZAP]) or to the bacterial chemoattractant FMLP. When chemotaxis was studied in a modified Boyden chamber, physiologic concentrations of adenosine promoted chemotaxis by as much as 60%. Adenosine receptor analogues, 5'N-ethylcarboxamidoadenosine (NECA) and N6-phenylisopropyladenosine (PIA), also promoted chemotaxis; the order of agonist potency was consistent with that of an A2 adenosine receptor (NECA greater than PIA greater than or equal to adenosine). A potent antagonist at adenosine receptors, 8-p-sulfophenyltheophylline (10 microM), completely reversed NECA enhancement of chemotaxis but did not affect chemotaxis by itself. Neither NECA nor 2-chloroadenosine, a nonselective adenosine receptor agonist, alone was chemotactic or chemokinetic by checkerboard analysis. NECA also promoted chemotaxis quantitated by a different technique, chemotaxis under agarose, to the surrogate bacterial chemoattractant FMLP. These data suggest that engagement of adenosine A2 receptors uniquely modulates neutrophil function so as to promote migration of neutrophils to sites of tissue damage while preventing the neutrophils from injuring healthy tissues en route.
Rose
F R
FR
Department of Medicine, New York University Medical Center, New York, New York 10016.
Hirschhorn
R
R
Weissmann
G
G
Cronstein
B N
BN
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000187:drug effects; D013268:Stimulation, Chemical; D013481:Superoxides / Q000096:biosynthesis; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D011983:Receptors, Purinergic; D013481:Superoxides; D019830:Adenosine-5'-(N-ethylcarboxamide); D009240:N-Formylmethionine Leucyl-Phenylalanine; C031433:8-(4-sulfophenyl)theophylline; D015054:Zymosan; D013806:Theophylline; D000241:Adenosine