Role of leukocyte adhesion molecules in complement-induced lung injury.
The bolus i.v. infusion of cobra venom factor into rats results in acute lung injury that is neutrophil-dependent, oxygen radical-mediated, and requires CD18. In our studies a more precise definition regarding the role of beta-integrins and requirements for cytokines was obtained by the use of blocking antibodies. Lung injury was quantitated by changes in permeability (leakage of 125I-BSA) and hemorrhage (extravasation of 51Cr-RBC). In animals treated with anti-CD11a, the permeability and hemorrhage parameters were reduced by 30 and 29%, respectively. Treatment with anti-CD11b resulted in reductions in permeability and hemorrhage by 53 and 48%, respectively, whereas anti-intercellular adhesion molecule-1 reduced the parameters of injury by 60 and 75%, respectively. Not surprisingly, treatment with antibodies to very late Ag-4, TNF-alpha and IL-1 failed to show any protective effects, which contrasts to the requirements for these molecules in lung injury after deposition of IgG immune complexes. Protective interventions were associated with a reduction in lung content of myeloperoxidase. These studies indicate that, in the cobra venom factor model of acute lung injury in rats, engagement of Mac-1, lymphocyte function-associated Ag-1, and intercellular adhesion molecule-1 are essential, whereas, in contrast to other models of neutrophil mediated lung injury, cytokines (TNF-alpha and IL-1) and very late Ag-4 are not required for the full development of injury.
Mulligan
M S
MS
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Smith
C W
CW
Anderson
D C
DC
Todd
R F
RF
Miyasaka
M
M
Tamatani
T
T
Issekutz
T B
TB
Ward
P A
PA
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000936:Antigen-Antibody Complex / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D003165:Complement System Proteins / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004546:Elapid Venoms / Q000633:toxicity*; D016023:Integrins / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1; D007962:Leukocytes / Q000276:immunology*; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009195:Peroxidase / Q000187:drug effects / Q000276:immunology; D051381:Rats
D000906:Antibodies; D000936:Antigen-Antibody Complex; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004546:Elapid Venoms; D016023:Integrins; C016310:cobra venom factor; D018799:Intercellular Adhesion Molecule-1; D003165:Complement System Proteins; D009195:Peroxidase