Neutrophils enhance clearance of necrotic epithelial cells in ozone-induced lung injury in rhesus monkeys

To test the hypothesis that neutrophil influx is important for the removal of necrotic airway epithelial cells, rhesus monkeys were treated with a fun ction-blocking monoclonal antibody (MAb) against CD18 followed by exposure to ozone or filtered air. CD18 MAb-treated, ozone-exposed monkeys showed a significant inhibition of neutrophil emigration and an accumulation of necr otic airway epithelial cells. In a subsequent experiment, monkeys were give n CD18 MAb or an isotype control immunoglobulin before ozone or filtered-ai r exposure. Complement 5a was instilled into lobes of the right lung at the end of the exposure. Lavage neutrophils were significantly elevated in the right lobes compared with those in the contralateral left lobes; consequen tly, there were significantly fewer necrotic cells in the airways of the ri ght lung, whereas large aggregations of necrotic cells were observed in the contralateral airways of the left lung. These data indicate that neutrophi l influx in ozone-induced injury in primates is CD18 dependent and that neu trophils contribute to the repair of airway epithelium by removal of injure d epithelial cells.