CD18-INDEPENDENT MECHANISM OF NEUTROPHIL EMIGRATION IN THE RABBIT LUNG AFTER ISCHEMIA-REPERFUSION

Background. Reperfusion of ischemic lung causes an inflammatory pulmon ary vascular injury characterized by increased vascular permeability a nd migration of inflammatory cells into the alveoli. Migration of neut rophils into the alveolus during reperfusion after 24 hours of unilate ral pulmonary artery occlusion has been shown to be in part dependent on the CD18 adhesion molecule on the cell surface. The current study i nvestigated whether reperfusion lung injury after a 1-hour period of c omplete lung ischemia was CD18 dependent. Methods. Eighteen rabbits we re assigned to one of three groups. Groups 1 and 2 were subjected to o ne hour of in situ right hilar occlusion followed by 2 hours of reperf usion. Group 3 was subjected to identical surgical dissection but the right hilum was never occluded. Group 1 rabbits received saline soluti on (1 mL/kg) before hilar occlusion and group 2 rabbits, monoclonal an tibody 60.3, a blocking antibody for the CD18 adhesion molecule on the neutrophil surface (2 mg/kg). In 3 of the antibody-treated rabbits, f low cytometry was performed on blood neutrophils before and after admi nistration of the antibody and 120 minutes after reperfusion. Results. The rabbits in groups 1 and 2 had significantly increased alveolar ne utrophil infiltrate and increased pulmonary vascular resistance compar ed with the rabbits in group 3. However, there was no significant diff erence between group 1 (saline solution heated) and group 2 (antibody treated). Antibody treatment did not block migration of neutrophils in to the alveoli. Flow cytometry of circulating neutrophils demonstrated that CD18 was upregulated after reperfusion and that CD18 was fully b locked after antibody treatment for the duration of the study. Conclus ions. We conclude that a 1-hour period of warm ischemia followed by re perfusion results in upregulation of CD18 but that emigration of the n eutrophils into the alveoli is not CD18 dependent in this injury.