American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 16-20, (2002)
© 2002 American Thoracic Society
Adenosine Deaminase Inhibition Attenuates Microvascular Dysfunction and Improves Survival in Sepsis
Elliott S. Cohen,
William R. Law,
Cordus R. Easington,
Kenneth Q. Cruz,
Beth A. Nardulli,
Robert A. Balk,
Joseph E. Parrillo and
Steven M. Hollenberg
Section of Pulmonary and Critical Care Medicine and Section of Critical Care Medicine, Rush-Presbyterian-St. Lukes Medical Center; Department of Physiology and Biophysics, University of Illinois, Chicago, Illinois
Correspondence and requests for reprints should be addressed to Elliott S. Cohen, M.D., Section of Pulmonary and Critical Care Medicine, Suite 054, 1725 W. Harrison Street, Chicago, IL 60612. E-mail: ecohenus{at}yahoo.com
The ability of increased endogenous adenosine to mitigate microvascular derangements in sepsis was studied. Pentostatin (2'-deoxycoformycin), an inhibitor of adenosine deaminase, was administered to mice immediately after induction of sepsis by cecal ligation and puncture. Intravital video microscopy of cremasteric postcapillary venules was performed. Leukocyte rolling and adhesion were significantly increased in septic mice compared with control mice. Treatment of septic mice with pentostatin significantly decreased leukocyte rolling and adhesion (6.02 ± 0.09 versus 1.72 ± 0.12 rolling cells/min, 2.07 ± 0.04 versus 0.62 ± 0.05 adherent cells/100 µm per minute; p < 0.001). Albumin leakage (ratio) was significantly attenuated in septic animals treated with pentostatin (0.42 ± 0.05 versus 0.21 ± 0.04; p < 0.01). Circulating levels of interleukin-6, tumor necrosis factor- , and soluble tumor necrosis factor type II receptor were decreased in septic mice treated with pentostatin. Survival was significantly improved at 48 hours in mice treated with pentostatin. These results suggest an important role for adenosine in modulating both leukocyte-dependent and -independent mechanisms of endothelial injury in sepsis. Exploiting the advantageous action of endogenous adenosine represents a potentially useful and novel therapeutic approach for the treatment of sepsis.
Key Words: sepsis • adenosine • microvasculature • leukocyte • endothelium
This article has been cited by other articles:
|
|
|
|
 
H. T. Lee, M. Kim, J. D. Joo, G. Gallos, J.-F. Chen, and C. W. Emala
A3 adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis
Am J Physiol Regulatory Integrative Comp Physiol,
October 1, 2006;
291(4):
R959 - R969.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. R. Law
Adenosine receptors in the response to sepsis: what do receptor-specific knockouts tell us?
Am J Physiol Regulatory Integrative Comp Physiol,
October 1, 2006;
291(4):
R957 - R958.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. K. Eltzschig, M. Faigle, S. Knapp, J. Karhausen, J. Ibla, P. Rosenberger, K. C. Odegard, P. C. Laussen, L. F. Thompson, and S. P. Colgan
Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26
Blood,
September 1, 2006;
108(5):
1602 - 1610.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Eisenhut
Comment on "Pretreatment Intracerebral and Peripheral Blood Immune Responses in Vietnamese Adults with Tuberculous Meningitis: Diagnostic Value and Relationship to Disease Severity and Outcome"
J. Immunol.,
May 1, 2006;
176(9):
5137 - 5137.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. W. Sullivan, D. D. Lee, W. G. Ross, J. A. DiVietro, C. M. Lappas, M. B. Lawrence, and J. Linden
Activation of A2A adenosine receptors inhibits expression of {alpha}4/{beta}1 integrin (very late antigen-4) on stimulated human neutrophils
J. Leukoc. Biol.,
January 1, 2004;
75(1):
127 - 134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Tobin
Critical Care Medicine in AJRCCM 2002
Am. J. Respir. Crit. Care Med.,
February 1, 2003;
167(3):
294 - 305.
[Full Text]
[PDF]
|
|
|
Copyright © 2002 American Thoracic Society
|
|
|
