ROLE OF ALVEOLAR MACROPHAGE CHEMOTAXIS AND PHAGOCYTOSIS IN PULMONARY CLEARANCE RESPONSES TO INHALED PARTICLES - COMPARISONS AMONG RODENT SPECIES

Alveolar macrophages (AM) play an important role in clearing inhaled p articles from the lung. The mechanisms through which macrophages ident ify 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 materia ls. In previous studies, we assessed the mechanisms of macrophage-medi ated clearance of inhaled particles using a rat model. In this regard, it appears that one mechanism by which rat alveolar macrophages are r ecruited to sites of particle or fiber deposition is through complemen t activation and consequent generation of chemotactic factors by the i nhaled particulates. Whether this mechanism is operative in other rode nt species remains an unanswered question. The current studies were un dertaken to compare pulmonary clearance responses in several rodent sp ecies exposed to carbonyl iron (CI) particles. In vitro and in vivo pu lmonary clearance responses were evaluated using one strain each of mo use, hamster, rat, and guinea pig. In vitro studies showed that hamste r AM had the greatest phagocytic activity and that rat AM migrated bes t 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 deposition patterns i n the distal lung were nearly identical for all species, although enha nced numbers of CI particles were deposited on alveolar duct bifurcati ons of either rats or mice compared to hamsters, and particle depositi on in guinea pigs was substantially lower. Time course studies showed that enhanced numbers of rat AM migrated to deposition sites and phago cytized particles, and this correlated with increased numbers and perc entages of phagocytic macrophages recovered by lavage (P < 0.01). In v ivo phagocytic rates were the lowest in the mouse, and this correlated with reduced phagocytic rates in vitro. It is concluded from these st udies that the rat may be the most efficient rodent species in clearin g inhaled iron particles. In addition, it is conceivable that hamster AM are recruited to sites of particle deposition by a noncomplement-me diated mechanism. (C) 1993 Wiley-Liss, Inc.