|
|
||||||||
Department of Pathology, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131
Neutrophils are pivotal in the
pathogenesis of ischemia-reperfusion (I/R) injury leading to
muscle damage. Firm adhesion of neutrophils to the endothelium is
initiated by an interaction between intercellular adhesion molecular-1
(ICAM-1) on the endothelium and
2-integrins on
neutrophils. Inhibition of ICAM-1-dependent binding using monoclonal
antibodies has been shown to be efficacious in ameliorating I/R injury
by preventing the influx of neutrophils into the ischemic
tissue. We recently described a cyclic peptide that is a potent and
selective inhibitor of ICAM-1 (IP25) in vitro. In this study, we tested
the hypothesis that IP25-mediated blockade of ICAM-1 would inhibit
neutrophil influx during reperfusion of ischemic tissue and
consequently attenuate muscle injury in a tourniquet hindlimb murine
model of I/R injury. Varying amounts of peptide drug were injected at
the beginning of the reperfusion period. The neutrophil influx and size
of infarction at the end of 2 h of reperfusion were compared with
those in untreated control mice and contralateral nonischemic
limbs. Mice receiving IP25 immediately before reperfusion showed a 56%
reduction in neutrophil infiltration in the ischemic muscle,
accompanied by a 40% reduction in the infarct size. No effect on I/R
injury was seen if IP25 administration was delayed for 60 min after
reperfusion. We conclude that IP25 effectively inhibits ICAM-1-mediated
adhesion of neutrophils to the endothelium in mice leading to a
protective effect and suggests that synthetic peptide antagonists have
a potential role as therapeutic tools.
infarction; peptide antagonist; cell adhesion
This article has been cited by other articles:
![]() |
R. Ward, N. Souder, D. Stahl, F. Hunter, R. Probe, C. Chaput, and E. Childs The Role of Nitric Oxide Synthase and Heme Oxygenase in the Protective Effect of Hypothermia in Ischemia-Reperfusion Injury J. Bone Joint Surg. Am., November 1, 2009; 91(11): 2637 - 2645. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Dumont, P. Bouchard, and J. Frenette Neutrophil-induced skeletal muscle damage: a calculated and controlled response following hindlimb unloading and reloading Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1831 - R1838. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. A. O'Brien, S. Ling, E. Abbas, A. Dai, J. Zhang, W. C. Wang, A. Bensoussan, R. Luo, Z.-X. Guo, and P. A. Komesaroff A Chinese Herbal Preparation Containing Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum Reduces Circulating Adhesion Molecules Evid. Based Complement. Altern. Med., September 27, 2008; (2008) nen060v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Z. Behm, B. A. Kaufmann, C. Carr, M. Lankford, J. M. Sanders, C. E. Rose, S. Kaul, and J. R. Lindner Molecular Imaging of Endothelial Vascular Cell Adhesion Molecule-1 Expression and Inflammatory Cell Recruitment During Vasculogenesis and Ischemia-Mediated Arteriogenesis Circulation, June 3, 2008; 117(22): 2902 - 2911. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. G. Tidball Inflammatory processes in muscle injury and repair Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R345 - R353. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |