Effect of circulating neutrophil depletion on lung injury induced by inhaled silica particles.
Polymorphonuclear leukocytes (PMNs) recruited into the alveolar region during inflammation may injure the lung parenchyma by releasing cytotoxic oxygen radicals and proteases. Because brief exposures to crystalline silica elicit recruitment of PMNs into the alveolar region, which is strongly correlated with parameters of cytotoxicity, increased alveolar epithelial permeability, and lysosomal enzyme release, we sought to evaluate the potential role of PMNs in silica-induced lung injury. Rats were depleted of PMNs by administration of an anti-rat PMN antiserum prior to exposure to silica. Pulmonary inflammatory responses to silica in this group were compared to responses in normal silica-exposed rats as well as sham-exposed normal or PMN-depleted rats. Bronchoalveolar lavage fluids from normal, silica-exposed rats contained 9.7 x 10(6) PMNs immediately after exposure for 3 days, compared to 0.01 x 10(6) PMNs for both normal or PMN-depleted, sham-exposed rats. Bronchoalveolar lavage fluids from successfully PMN-depleted, exposed rats contained significantly fewer (0.7 x 10(6)) PMNs compared to normal silica-exposed rats. In both groups of silica-exposed rats, a variety of biochemical indicators of lung injury were increased significantly compared to measurements from both sham-exposed groups, but there were no differences between PMN-depleted and normal silica-exposed groups. The results suggest that recruitment of PMNs into the alveolar region is not a necessary prerequisite for the observed increases in biochemical indicators of silica-induced acute lung injury.
Gavett
S H
SH
Central Research and Development, E.I. du Pont de Nemours & Co., Newark, Delaware 19714.
Carakostas
M C
MC
Belcher
L A
LA
Warheit
D B
DB
D000118:Acetylglucosaminidase / Q000378:metabolism; D000280:Administration, Inhalation; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000201:enzymology / Q000378:metabolism; D002199:Capillary Permeability; D005353:Fibronectins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D008171:Lung Diseases / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D016676:Macrophages, Alveolar / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000098:blood supply; D051381:Rats; D011919:Rats, Inbred Strains; D012822:Silicon Dioxide / Q000633:toxicity*
D005353:Fibronectins; D011506:Proteins; D012822:Silicon Dioxide; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D000118:Acetylglucosaminidase