Alteration in lung particle translocation, macrophage function, and microfilament arrangement in monocrotaline-treated rats

Individuals with preexisting cardiopulmonary disease are thought to be more susceptible to acute episodes of particulate pollution resulting in increa sed morbidity and mortality. Our study was designed to evaluate particle fa te and macrophage function in an animal model of monocrotaline (MCT)-induce d pulmonary hypertension. Two weeks following a single MCT injection, Sprag ue-Dawley rats were exposed sequentially to two different colored fluoresce nt microspheres 1.0 mu m in diameter by aerosolization. Morphometric evalua tion of lung sections was performed 0 and 24 h following the final particle exposure to determine the intrapulmonary location of inhaled microspheres. A decrease in the number of particles phagocytized by alveolar macrophages and an increase of free particles overlying the epithelium were found in M CT-treated animals compared with control. Pulmonary macrophages recovered b y bronchoalveolar lavage were evaluated for chemotactic and phagocytic abil ity. Macrophage chemotaxis was significantly impaired following MCT treatme nt compared with controls, whereas phagocytic activity of macrophages lavag ed from MCT and control treatment groups was similar. Macrophages were stai ned for filamentous (F) and globular (G) actin using Texas-Red-labeled phal loidin and Oregon-green-labeled DNase I, respectively. The area of microfil ament staining for F and G actin increased, but the ratio of F/G actin was significantly decreased in animals with MCT treatment compared with control . While the responses observed with MCT treatment, such as pulmonary edema, polymorphonuclear leukocytes influx, and unique macrophage morphology may contribute to impaired macrophage function, the change in microfilament arr angement suggests that MCT may inhibit macrophage chemotaxis and impair par ticle clearance from the lungs. (C) 1998 Academic Press.