Response of rat alveolar macrophages to ozone: quantitative assessment of population size, morphology, and proliferation following acute exposure.
The purpose of this study was to evaluate the in vivo effects of an acute exposure to low levels of ozone on rat pulmonary alveolar macrophages (PAM). Fisher 344 rats exposed to 0.0, 0.12, 0.8, or 1.5 ppm O3 for 6 h were killed immediately after and 3, 18, 42, or 66 h after ozone exposure and their lungs were lavaged. Compared to sham-exposed (control) rats, exposure to 0.12 ppm O3 had no measurable effect on the total number, labeling index (LI), mitotic index (MI), or morphology of rat alveolar macrophages. The number of neutrophils was significantly (p less than or equal to 0.001) greater than in controls at 3, 18, and 42 h after exposure to 1.5 ppm O3 and 42 h after exposure to 0.8 ppm O3. The number of PAM was approximately twice that of controls 42 and 66 h after exposure to 0.8 and 1.5 ppm O3. There was a significant (p less than or equal to 0.001) increase in PAM MI 42 and 66 h after exposure to 1.5 ppm O3 and 42 h after 0.8 ppm O3. The increase in the number of PAM in mitosis was preceded by an increase in PAM LI. The PAM LI was significantly (p less than or equal to 0.001) greater than controls 18 and 42 h after exposure but returned to near normal levels by 66 h after exposure. There was a transient decrease in the mean nuclear/cytoplasmic ratio of PAM from rats exposed to 1.5 ppm O3 18 and 42 h after exposure due to an increase in the mean PAM cytoplasmic area. Comparison of the PAM population doubling time (Dt) and cell cycle time (Ct) suggest that PAM proliferation played a significant role in the observed increase in PAM following exposure to 0.8 and 1.5 ppm O3. These results highlight the dynamic response of PAM to an acute exposure to ozone and suggest that the proliferative response of pulmonary alveolar macrophages may be a useful indicator of pulmonary damage following inhalation of an irritant oxidant.
Hotchkiss
J A
JA
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Harkema
J R
JR
Kirkpatrick
D T
DT
Henderson
R F
RF
D000818:Animals; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010126:Ozone / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D010126:Ozone; D004247:DNA