Adenosine inhibits ischemia-reperfusion-induced leukocyte adherence and extravasation.
Ischemia and reperfusion (I/R) of the small intestine initiates a series of events that result in neutrophil-mediated microvascular injury. Recent reports suggest that adenosine possesses anti-inflammatory properties by virtue of its ability to inhibit neutrophil (PMN) superoxide (O2-.) and hydrogen peroxide (H2O2) production and to interfere with PMN adherence to cultured endothelium. In an attempt to further characterize the anti-inflammatory properties of adenosine in vivo we assessed the influence of exogenous adenosine on 1) I/R-induced PMN-mediated microvascular injury in the feline small intestine, 2) feline PMN superoxide production, and 3) I/R-induced PMN adherence to feline mesenteric venular endothelium. We found that intra-arterial administration of adenosine (2 microM) significantly attenuated the I/R-induced increases in intestinal capillary permeability. This protective effect of adenosine could not be explained entirely on its ability to inhibit PMN O2-. (or H2O2) production, since adenosine was effective in inhibiting feline PMN O2-. production by only 20%. Using intravital microscopic techniques in cat mesentery, we found that adenosine did not alter the responses of venular blood flow, shear rate, leukocyte rolling velocity, and leukocyte adherence to I/R when compared with control animals. However, the number of extravasated leukocytes during the ischemic period was significantly reduced by adenosine. Adenosine reduced the number of adherent leukocytes by 25% at 10 and 60 min of reperfusion while leukocyte extravasation was reduced by 65-70% during the same period. Our data indicate that the adenosine-induced suppression of leukocyte extravasation cannot be explained solely by an attenuation in leukocyte adherence to venular endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Grisham
M B
MB
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130.
Hernandez
L A
LA
Granger
D N
DN
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability; D002415:Cats; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D006098:Granulocytes / Q000378:metabolism; D007421:Intestine, Small / Q000098:blood supply*; D007511:Ischemia / Q000473:pathology*; D007962:Leukocytes / Q000502:physiology*; D015424:Reperfusion; D013481:Superoxides / Q000378:metabolism; D014699:Venules
D013481:Superoxides; D000241:Adenosine