CD18-independent mechanism of neutrophil emigration in the rabbit lung after ischemia-reperfusion.
BACKGROUND
Reperfusion of ischemic lung causes an inflammatory pulmonary vascular injury characterized by increased vascular permeability and migration of inflammatory cells into the alveoli. Migration of neutrophils into the alveolus during reperfusion after 24 hours of unilateral pulmonary artery occlusion has been shown to be in part dependent on the CD18 adhesion molecule on the cell surface. The current study investigated whether reperfusion lung injury after a 1-hour period of complete lung ischemia was CD18 dependent.


METHODS
Eighteen rabbits were assigned to one of three groups. Groups 1 and 2 were subjected to one hour of in situ right hilar occlusion followed by 2 hours of reperfusion. Group 3 was subjected to identical surgical dissection but the right hilum was never occluded. Group 1 rabbits received saline solution (1 mL/kg) before hilar occlusion and group 2 rabbits, monoclonal antibody 60.3, a blocking antibody for the CD18 adhesion molecule on the neutrophil surface (2 mg/kg). In 3 of the antibody-treated rabbits, flow cytometry was performed on blood neutrophils before and after administration of the antibody and 120 minutes after reperfusion.


RESULTS
The rabbits in groups 1 and 2 had significantly increased alveolar neutrophil infiltrate and increased pulmonary vascular resistance compared with the rabbits in group 3. However, there was no significant difference between group 1 (saline solution treated) and group 2 (antibody treated). Antibody treatment did not block migration of neutrophils into the alveoli. Flow cytometry of circulating neutrophils demonstrated that CD18 was upregulated after reperfusion and that CD18 was fully blocked after antibody treatment for the duration of the study.


CONCLUSIONS
We conclude that a 1-hour period of warm ischemia followed by reperfusion results in upregulation of CD18 but that emigration of the neutrophils into the alveoli is not CD18 dependent in this injury.
Department of Cardiothoracic Surgery, University of Washington, Seattle, USA.
D D
DD
Thomas
S R
SR
Sharar
R K
RK
Winn
E Y
EY
Chi
E D
ED
Verrier
M D
MD
Allen
M J
MJ
Bishop
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018821:CD18 Antigens / Q000276:immunology*; D002465:Cell Movement; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008168:Lung / Q000098:blood supply*; D016040:Lung Transplantation / Q000009:adverse effects; D018375:Neutrophil Activation / Q000276:immunology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D013997:Time Factors; D014655:Vascular Resistance
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens