Role of beta 2 integrins and ICAM-1 in lung injury following ischemia-reperfusion of rat hind limbs.
Ischemia/reperfusion involving the hind limbs of rats results in both local injury to skeletal muscle as well as injury to lungs, as measured by increased vascular permeability (125I-labeled bovine serum albumin leakage) and hemorrhage (extravasation of 51Cr-labeled rat erythrocytes). In the current study, we have focused on events in lungs occurring during reperfusion of hind limbs. Analysis of blood neutrophils obtained 4 hours after reperfusion has indicated up-regulation of CD11b and CD18 but not CD11a. Plasma from the same animals demonstrate the ability to induce similar effects in normal blood neutrophils, indicative of the presence of a neutrophil-activating agent in plasma. During reperfusion, lung injury, which develops progressively over a 4-hour period, has been shown to be neutrophil-dependent and requires CD11a/CD18 and CD11b/CD18 as well as intercellular adhesion molecule-1. These data suggest that ischemia and reperfusion injury of rat lower extremities causes systemic changes that result in neutrophil-dependent lung injury that is beta 2 integrin- (leukocyte function antigen-1, Mac-1) and intercellular adhesion molecule-1-dependent.
Seekamp
A
A
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Mulligan
M S
MS
Till
G O
GO
Smith
C W
CW
Miyasaka
M
M
Tamatani
T
T
Todd
R F
RF
Ward
P A
PA
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D018845:CD11 Antigens; D018821:CD18 Antigens; D002199:Capillary Permeability; D015815:Cell Adhesion Molecules / Q000502:physiology*; D006470:Hemorrhage / Q000378:metabolism / Q000473:pathology; D006614:Hindlimb / Q000098:blood supply; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1; D007511:Ischemia / Q000378:metabolism*; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism*; D015854:Up-Regulation
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1