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 function-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 necrotic airway epithelial cells. In a subsequent experiment, monkeys were given CD18 MAb or an isotype control immunoglobulin before ozone or filtered-air 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; consequently, there were significantly fewer necrotic cells in the airways of the right lung, whereas large aggregations of necrotic cells were observed in the contralateral airways of the left lung. These data indicate that neutrophil influx in ozone-induced injury in primates is CD18 dependent and that neutrophils contribute to the repair of airway epithelium by removal of injured epithelial cells.
Hyde
D M
DM
California Regional Primate Research Center and Center for Comparative Respiratory Biology and Medicine, University of California, Davis, California 95616, USA. dmhyde@ucdavis.edu
Miller
L A
LA
McDonald
R J
RJ
Stovall
M Y
MY
Wong
V
V
Pinkerton
K E
KE
Wegner
C D
CD
Rothlein
R
R
Plopper
C G
CG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000032:analysis; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D015936:Complement C5a / Q000276:immunology; D004847:Epithelial Cells / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology*; D008253:Macaca mulatta; D008297:Male; D018613:Microscopy, Confocal; D009336:Necrosis; D009504:Neutrophils / Q000276:immunology*; D010083:Oxidants, Photochemical / Q000009:adverse effects*; D010126:Ozone / Q000009:adverse effects*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D010083:Oxidants, Photochemical; D010126:Ozone; D015936:Complement C5a; D001973:Bromodeoxyuridine