Role of neutrophil adherence receptors (CD 18) in lung permeability following lower torso ischemia.
Ischemia and reperfusion of the lower torso lead to leukotriene- and neutrophil (PMN)-dependent lung injury characterized by lung PMN sequestration, increased permeability, and noncardiogenic edema. It is thought that PMNs require adhesion to endothelium to alter barrier function. This study tests the role of CD 18, the PMN adherence receptor, in mediating lung permeability after lower torso ischemia and reperfusion. Anesthetized rabbits (n = 9) underwent 3 hours of bilateral hind limb ischemia. Ten minutes after the release of the tourniquets, plasma leukotriene B4 levels increased to 395 +/- 85 pg/ml, higher than 129 +/- 35 pg/ml in controls (n = 9, p less than 0.01). At this time there was a reduction in circulating white blood cells (x 10(3)), 3.56 +/- 0.49/mm3 relative to 6.07 +/- 0.61/mm3 in controls (p less than 0.01). PMNs were sequestered in the hind limbs, indicated by increased myeloperoxidase activity of 1.06 +/- 0.19 units/g compared with 0.56 +/- 0.09 units/g in controls (p less than 0.05). Four hours after tourniquet release, PMNs were sequestered in the lungs, 52 +/- 4 PMNs per 10 high-power fields, a value higher than 31.5 +/- 3 PMNs per 10 high-power fields in controls; bronchoalveolar lavage fluid protein content increased to 554 +/- 90 micrograms/ml relative to 277 +/- 46 micrograms/ml in controls; and there was lung edema, measured by increased wet weight-to-dry weight ratios of 5.19 +/- 0.10, higher than 4.29 +/- 0.21 in controls (all p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
R
R
Welbourn
G
G
Goldman
L
L
Kobzik
I S
IS
Paterson
C R
CR
Valeri
D
D
Shepro
H B
HB
Hechtman
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D018821:CD18 Antigens; D002199:Capillary Permeability / Q000502:physiology*; D006614:Hindlimb / Q000098:blood supply* / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011652:Pulmonary Circulation; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D015424:Reperfusion; D014111:Tourniquets
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion; D009195:Peroxidase