Reduction of postischemic leukocyte-endothelium interaction by adenosine via A2 receptor.
The adhesion of leukocytes to the endothelium of postcapillary venules hallmarks a key event in ischemia-reperfusion injury. Adenosine has been shown to protect from postischemic reperfusion injury, presumably through inhibition of postischemic leukocyte-endothelial interaction. This study was performed to investigate in vivo by which receptors the effect of adenosine on postischemic leukocyte-endothelium interaction is mediated. The hamster dorsal skinfold model and fluorescence microscopy were used for intravital investigation of red cell velocity, vessel diameter, and leukocyte-endothelium interaction in postcapillary venules of a thin striated skin muscle. Leukocytes were stained in vivo with acridine orange (0.5 mg kg-1 min-1 i.v.). Parameters were assessed prior to induction of 4 h ischemia to the muscle tissue and 0.5 h, 2 h, and 24 h after reperfusion. Adenosine, the adenosine A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA), the A2-selective agonist CGS 21,680, the non-selective adenosine receptor antagonist xanthine amine congener (XAC), and the adenosine uptake blocker S-(p-nitrobenzyl)-6-thioinosine (NBTI) were infused via jugular vein starting 15 min prior to release of ischemia until 0.5 h after reperfusion. Adenosine and CGS 21,680 significantly reduced postischemic leukocyte-endothelium interaction 0.5 h after reperfusion (p less than 0.01), while no inhibitory effect was observed with CCPA. Coadministration of XAC blocked the inhibitory effects of adenosine. Infusion of NBTI alone effectively decreased postischemic leukocyte-endothelium interaction. These findings indicate that adenosine reduces post-ischemic leukocyte-endothelium interaction via A2 receptor and suggest a protective role of endogenous adenosine during ischemia-reperfusion.
Nolte
D
D
Institute for Surgical Research, University of Munich, Federal Republic of Germany.
Lorenzen
A
A
Lehr
H A
HA
Zimmer
F J
FJ
Klotz
K N
KN
Messmer
K
K
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D007511:Ischemia / Q000473:pathology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008647:Mesocricetus; D009132:Muscles / Q000098:blood supply*; D010627:Phenethylamines / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology*; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D010627:Phenethylamines; D011983:Receptors, Purinergic; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C058394:2-chloro-N(6)cyclopentyladenosine; D013868:Thioinosine; C051869:8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine; C001789:4-nitrobenzylthioinosine; D000241:Adenosine