Ozone-induced inflammation in the lower airways of human subjects.
Although ozone (O3) has been shown to induce inflammation in the lungs of animals, very little is known about its inflammatory effects on humans. In this study, 11 healthy nonsmoking men, 18 to 35 yr of age (mean, 25.4 +/- 3.5), were exposed once to 0.4 ppm O3 and once to filtered air for 2 h with intermittent exercise. Eighteen hours later, bronchoalveolar lavage (BAL) was performed and the cells and fluid were analyzed for various indicators of inflammation. There was an 8.2-fold increase in the percentage of polymorphonuclear leukocytes (PMN) in the total cell population, and a small but significant decrease in the percentage of macrophages after exposure to O3. Immunoreactive neutrophil elastase often associated with inflammation and lung damage increased by 3.8-fold in the fluid while its activity increased 20.6-fold in the lavaged cells. A 2-fold increase in the levels of protein, albumin, and IgG suggested increased vascular permeability of the lung. Several biochemical markers that could act as chemotactic or regulatory factors in an inflammatory response were examined in the BAL fluid (BALF). The level of complement fragment C3 alpha was increased by 1.7-fold. The chemotactic leukotriene B4 was unchanged while prostaglandin E2 increased 2-fold. In contrast, three enzyme systems of phagocytes with potentially damaging effects on tissues and microbes, namely, NADPH-oxidase and the lysosomal enzymes acid phosphatase and beta-glucuronidase, were increased neither in the lavaged fluid nor cells. In addition, the amounts of fibrogenic-related molecules were assessed in BALF.(ABSTRACT TRUNCATED AT 250 WORDS)
Koren
H S
HS
Inhalation Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Devlin
R B
RB
Graham
D E
DE
Mann
R
R
McGee
M P
MP
Horstman
D H
DH
Kozumbo
W J
WJ
Becker
S
S
House
D E
DE
McDonnell
W F
WF
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000166:cytology; D001999:Bronchoscopy; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D008297:Male; D010126:Ozone / Q000009:adverse effects*; D011014:Pneumonia / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D013997:Time Factors
D015415:Biomarkers; D010126:Ozone