Role of alveolar macrophage chemotaxis and phagocytosis in pulmonary clearance responses to inhaled particles: comparisons among rodent species

Abstract

Alveolar macrophages (AM) play an important role in clearing inhaled particles from the lung. The mechanisms through which macrophages identify particles that have been deposited in the alveolar regions is not well understood, although macrophage motility and phagocytic functions appear to be prerequisites for efficient clearance of inhaled materials. In previous studies, we assessed the mechanisms of macrophage-mediated clearance of inhaled particles using a rat model. In this regard, it appears that one mechanism by which rat alveolar macrophages are recruited to sites of particle or fiber deposition is through complement activation and consequent generation of chemotactic factors by the inhaled particulates. Whether this mechanism is operative in other rodent species remains an unanswered question. The current studies were undertaken to compare pulmonary clearance responses in several rodent species exposed to carbonyl iron (CI) particles. In vitro and in vivo pulmonary clearance responses were evaluated using one strain each of mouse, hamster, rat, and guinea pig. In vitro studies showed that hamster AM had the greatest phagocytic activity and that rat AM migrated best to complement-dependent chemotactic factors. Subsequently, groups of animals from each species were exposed to CI particles for 1 or 6 hr at aerosol concentrations of 100 mg/m3. Particle depositions patterns in the distal lung were nearly identical for all species, although enhanced numbers of CI particles were deposited on alveolar duct bifurcations of either rats or mice compared to hamsters, and particle deposition in guinea pigs was substantially lower. Time course studies showed that enhanced numbers of rat AM migrated to deposition sites and phagocytized particles, and this correlated with increased numbers and percentages of phagocytic macrophages recovered by lavage (P < 0.01). In vivo phagocytic rates were the lowest in the mouse, and this correlated with reduced phagocytic rates in vitro. It is concluded from these studies that the rat may be the most efficient rodent species in clearing inhaled iron particles. In addition, it is conceivable that hamster AM are recruited to sites of particle deposition by a noncomplement-mediated mechanism.