Free lung cell response of mice and rats to mainstream cigarette smoke exposure

Abstract

Male C57BL mice and F-344 rats were exposed through nose only to fresh mainstream smoke from one University of Kentucky Reference cigarette (2R1) daily under standardized conditions. At different exposure points, the lungs of room control (RM), sham control (SH), and smoke-exposed (SM) animals were lavaged and the number, composition, and properties of bronchoalveolar lavage (BAL) cells were studied. Significantly elevated levels of blood COHb and pulmonary aryl hydrocarbon hydroxylase activity indicated effective inhalation of smoke by animals. The BAL cell analysis showed that cigarette smoke induced a five- to sevenfold increase in the number of BAL cells in mice following 10- to 12-week exposure. The proportion of neutrophils (PMN) increased to about 18±3% in SM mice as compared to <1% in controls. Cessation of smoke treatments returned the PMN levels to those of controls within 5 weeks. Unlike mice, smoke exposure for up to 32 weeks failed to induce appreciable changes in the number and proportion of macrophages and neutrophils in rats. Large brown macrophages were observed in SM groups of both species. Functional analysis demonstrated that the BAL cells from SM mice but not rats released greater amounts of superoxides than controls under resting and phagocytically stimulated conditions. Enzymatic analysis of macrophages showed that the activity of N-acetyllucosaminidase was increased in SM groups of both species. The activity of 5′ nucleotidase was significantly reduced in macrophages from SM mice but not rats. Activity of leucine aminopeptidase remained unaltered in both species. These results demonstrate distinct differences in the response of mice and rats to identically generated cigarette smoke.