title: Inhibition of white blood cell adhesion at reperfusion decreases tissue damage in postischemic striated muscle.
abstract: OBJECTIVE
  To determine the impact of white blood cell (WBC)-endothelium adhesion on tissue damage in the setting of ischemia-reperfusion injury in striated muscle.
  
  
  METHODS
  The cremaster muscle of four groups of anesthetized Sprague-Dawley rats was subjected to 4 hours of global, warm (37 degrees C) ischemia and 2 hours of reperfusion. At reperfusion two groups of animals received intravenous injections of monoclonal antibodies directed against either CD11b/CD18 (1B6) or ICAM-1 (1A29). The remaining two groups of animals received saline injections (NoRx) or nonreactive IgG1. In vivo light microscopic techniques were used to determine WBC adherence (number of WBCs per 100 microns postcapillary venules) at different intervals of reperfusion. Muscle viability was assessed with computer-assisted image analysis by measuring the optical intensity of transilluminated muscles after incubation with nitroblue tetrazolium.
  
  
  RESULTS
  Our results (mean +/- SEM) demonstrate a significant increase in the number of adherent WBCs relative to baseline (8.0 +/- 0.5) after 4 hours of global ischemia in animals receiving NoRx or IgG1. The significant increase occurred at 30 minutes of reperfusion (17.6 +/- 0.6 and 17.4 +/- 0.4 for NoRx or IgG1, respectively) and was sustained for the duration of the experiment. This increase in adherence was attenuated by 1B6 and 1A29 (12.2 +/- 2.2 and 12.4 +/- 0.8, respectively; p < 0.05 compared with NoRx and IgG1). The decrease in WBC adhesion was associated with a decrease in reperfusion injury to the muscle, as indicated by lower optical intensity values for the 1B6 and 1A29 groups (123 +/- 3 and 129 +/- 2) compared with the NoRx and IgG1 groups (151 +/- 2 and 158 +/- 4).
  
  
  CONCLUSIONS
  Our data support an important role for WBCs in the pathogenesis of ischemia-reperfusion injury. Interfering with the WBC-endothelium interactions by using monoclonal antibodies directed against WBCs and endothelial cell adhesion molecules may help to limit ischemia-reperfusion injury.
authors: Department of Physiology, UMDNJ-New Jersey Medical School, Newark 07103-2714, USA.
authors: R J
authors: RJ
authors: Ferrante
authors: R W
authors: RW
authors: Hobson
authors: M
authors: M
authors: Miyasaka
authors: D N
authors: DN
authors: Granger
authors: W N
authors: WN
authors: Durán
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D018845:CD11 Antigens / Q000276:immunology / Q000502:physiology; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D007074:Immunoglobulin G / Q000627:therapeutic use; D007202:Indicators and Reagents; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology; D007962:Leukocytes / Q000502:physiology*; D018715:Microscopy, Video; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology*; D009580:Nitroblue Tetrazolium; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D012965:Sodium Chloride / Q000008:administration & dosage; D014022:Tissue Survival; D014172:Transillumination
chemical_list: D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D007074:Immunoglobulin G; D007202:Indicators and Reagents; D018799:Intercellular Adhesion Molecule-1; D009580:Nitroblue Tetrazolium; D012965:Sodium Chloride