Species variation in the mechanism of killing of inhaled pneumococci

Detailed studies in murine models show inhaled staphylococci are killed mainly by alveolar macrophages. Recently, using histology and lung lavage to determine the site of killing of inhaled 59Fe-labeled pneumococci in rats, we found unexpectedly that most of the organisms were killed extracellularly. In the present studies we compared clearance of inhaled 59Fe-pneumococci in rats, guinea pigs, and rabbits to determine if extracellular killing of pneumococci is species-dependent. Absolute clearance rates were measured using Andersen plates. lung lavage and differential centrifugation were used to measure leukocyte-associated and free 59Fe-pneumococci and nonsedimentable 59Fe. Clearance was rapid in all species but was fastest in rabbits, which killed pneumococci almost as quickly as they were deposited (p less than 0.025 versus rats and guinea pigs). At 1-1/2 hours after pneumococcal deposition in rats, when clearance had reached 92%, alveolar macrophages contained only 31% of the total 59Fe while 56% was in the nonsedimentable, extracellular fraction. At 1-1/2 hours in guinea pigs, when clearance was 96% complete, macrophages contained 51% of the 59Fe and 34% was nonsedimentable (p less than 0.002 versus rats). In rabbits at 1-1/2 hours, macrophages had 94% of the 59Fe and only 4% was nonsedimentable (p less than 0.001 versus the other species). In no species were opsonic antibodies detected in sera or concentrated lavage. In vitro, rabbit and guinea pig alveolar macrophages killed pneumococci opsonized with both specific antibody and fresh serum, while rat macrophages had little activity (p less than 0.001). We conclude that the role of alveolar macrophages in killing inhaled pneumococci varies in different species.