A Mac-1 antibody reduces liver and lung injury but not neutrophil sequestration after intestinal ischemia-reperfusion.
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.
Hill
J
J
Department of Surgery at Brigham and Women's Hospital, Boston, MA 02115.
Lindsay
T
T
Rusche
J
J
Valeri
C R
CR
Shepro
D
D
Hechtman
H B
HB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D018845:CD11 Antigens; D002199:Capillary Permeability; D007422:Intestines / Q000098:blood supply* / Q000473:pathology; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology; D008099:Liver / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D011652:Pulmonary Circulation; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens