ABSTRACT
Our previous studies show that Bcl-2, a regulator of apoptosis, may be involved in the reduction of mucous cell metaplasia (MCM) during recovery from inflammatory responses. The present study was to determine whether neutrophilic inflammation mediates Bcl-2 expression in mucous cells. Rats were intratracheally instilled with 50-1000 microg of LPS. The number of neutrophils recovered by bronchoalveolar lavage (BAL) increased with the dose of LPS, and the percentage of Bcl-2-expressing cells increased with the numbers of neutrophils in the BAL. Depletion of neutrophils did not reduce MCM, but the percentage of Bcl-2-positive cells increased 1.8-fold in neutrophil-depleted compared with controls. Injection of rats with bezafibrate, an inducer of cytochrome P-450, doubled the number of neutrophils in the BAL, decreased MCM twofold compared with vehicle-injected controls, and reduced Bcl-2 expression. Bcl-2 mRNA levels decreased in a tracheal epithelial cell line treated with bezafibrate. These data demonstrate that Bcl-2 expression is independent of the number of neutrophils in the BAL and that bezafibrate may directly reduce Bcl-2 expression in epithelial cells.
Subject(s)
Inflammation/pathology , Lipopolysaccharides/toxicity , Neutrophils/physiology , Proto-Oncogene Proteins c-bcl-2/genetics , Animals , Bezafibrate/pharmacology , Bronchoalveolar Lavage Fluid/cytology , DNA Primers , Dose-Response Relationship, Drug , Genes, bcl-2/drug effects , Hypolipidemic Agents/pharmacology , Inflammation/genetics , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/physiology , Male , Metaplasia , Neutrophils/drug effects , Polymerase Chain Reaction , Rats , Rats, Inbred BN , Rats, Inbred F344 , Time Factors , Transcription, Genetic/drug effectsABSTRACT
Wood smoke is a significant source of air pollution in many parts of the United States, and epidemiological data suggest a causal relationship between elevated wood smoke levels and health effects. The present study was designed to provide information on the potential respiratory health responses to subchronic wood smoke exposures in a Native American community in New Mexico. Therefore, this study used the same type of wood under similar burning conditions and wood smoke particle concentrations to mimic the conditions observed in this community. Brown Norway rats were exposed 3 h/day, 5 days/week for 4 or 12 weeks to air as control, or to 1 or 10 mg/m3 concentrations of wood smoke particles from pinus edulis. The wood smoke consisted of fine particles (< 1 microm) that formed larger chains and aggregates having a size distribution of 63-74% in the < 1-microm fraction and 26-37% in the > 1-microm fraction. The particle-bound material was primarily composed of carbon, and the majority of identified organic compounds consisted of sugar and lignin derivatives. Pulmonary function, specifically carbon monoxide-diffusing capacity and pulmonary resistance, was somewhat affected in the high-exposure group. Mild chronic inflammation and squamous metaplasia were observed in the larynx of the exposed groups. The severity of alveolar macrophage hyperplasia and pigmentation increased with smoke concentration and length of exposure, and the alveolar septae were slightly thickened. The content of mucous cells lining the airways changed from Periodic Acid Schiff- to Alcian Blue-positive material in the low-exposure group after 90 days. Together, these observations suggest that exposure to wood smoke caused minor but significant changes in Brown Norway rats. Further studies are needed to establish whether exposure to wood smoke exacerbates asthmalike symptoms that resemble those described for children living in homes using wood stoves for heating and cooking.
