BACKGROUND: Intestinal ischemia and reperfusion (I/R) result in leukosequestration and injury to the liver and lungs. The adherence-dependent oxidative burst of neutrophils requires cell adhesion through the Mac-1 integrin. Neutrophil-mediated tissue injury may depend on this specific cell adhesion event. This study tests the effect of a Mac-1 (CD 11b) monoclonal antibody (MAb) (R17) on liver and lung injury after intestinal I/R. METHODS: After collaterals were ligated in anesthetized rats, the superior mesenteric artery was clamped for 60 minutes followed by 3 hours of reperfusion. Animals were treated with saline solution, R17, or nonspecific immunoglobulin M. Another nonischemic group of rats were sham controls. Lung and intestinal polymorphonuclear leukocyte sequestration was assessed by measurement of myeloperoxidase and lung permeability by bronchoalveolar lavage blood concentration ratio of 125I-labeled bovine serum albumin. RESULTS: At 3 hours of reperfusion lung and intestinal myeloperoxidase and lung permeability were increased. Treatment with R17 MAb did not reduce intestinal or lung myeloperoxidase but prevented increased lung permeability. Similarly, after treatment with saline solution, liver polymorphonuclear leukocyte sequestration increased after 3 hours of reperfusion, and serum alanine aminotransferase level rose eightfold. R17 MAb did not significantly reduce liver neutrophil sequestration; however, it reduced alanine aminotransferase level more than 50% when compared to saline solution controls. At 3 hours of reperfusion there was a leukocytosis (white blood cell count, 14.9 +/- 1.0 x 10(3)/mm3 vs 6.0 +/- 0.8 in sham [p less than 0.05]). The white blood cell count was unaffected by R17 MAb. CONCLUSIONS: These data indicate that a MAb to the neutrophil Mac-1 integrin reduces lung and liver injury after intestinal I/R but does not reduce lung or intestinal leukosequestration.
BACKGROUND: Intestinal ischemia and reperfusion (I/R) result in leukosequestration and injury to the liver and lungs. The adherence-dependent oxidative burst of neutrophils requires cell adhesion through the Mac-1 integrin. Neutrophil-mediated tissue injury may depend on this specific cell adhesion event. This study tests the effect of a Mac-1 (CD 11b) monoclonal antibody (MAb) (R17) on liver and lung injury after intestinal I/R. METHODS: After collaterals were ligated in anesthetized rats, the superior mesenteric artery was clamped for 60 minutes followed by 3 hours of reperfusion. Animals were treated with saline solution, R17, or nonspecific immunoglobulin M. Another nonischemic group of rats were sham controls. Lung and intestinal polymorphonuclear leukocyte sequestration was assessed by measurement of myeloperoxidase and lung permeability by bronchoalveolar lavage blood concentration ratio of 125I-labeled bovine serum albumin. RESULTS: At 3 hours of reperfusion lung and intestinal myeloperoxidase and lung permeability were increased. Treatment with R17 MAb did not reduce intestinal or lung myeloperoxidase but prevented increased lung permeability. Similarly, after treatment with saline solution, liver polymorphonuclear leukocyte sequestration increased after 3 hours of reperfusion, and serum alanine aminotransferase level rose eightfold. R17 MAb did not significantly reduce liver neutrophil sequestration; however, it reduced alanine aminotransferase level more than 50% when compared to saline solution controls. At 3 hours of reperfusion there was a leukocytosis (white blood cell count, 14.9 +/- 1.0 x 10(3)/mm3 vs 6.0 +/- 0.8 in sham [p less than 0.05]). The white blood cell count was unaffected by R17 MAb. CONCLUSIONS: These data indicate that a MAb to the neutrophil Mac-1 integrin reduces lung and liver injury after intestinal I/R but does not reduce lung or intestinal leukosequestration.
Authors: Madeleine Valdes Pahl; Nosratola D Vaziri; Timothy Connall; Debra Morrison; Choong Kim; Charles J Kaupke; Samuel E Wilson Journal: J Natl Med Assoc Date: 2005-02 Impact factor: 1.798
Authors: Liliane Benkoel; Frank Dodero; Jean Hardwigsen; Anne Marie Benoliel; Pierre Bongrand; Danielle Botta-Fridlund; Yves Patrice Le Treut; Albert Chamlian; Dominique Lombardo Journal: Dig Dis Sci Date: 2003-11 Impact factor: 3.199