Inhibition of rat alveolar macrophage phagocytic function by a Pseudomonas cepacia lipase

Abstract

The effects of purified Pseudomonas cepacia lipase on rat pulmonary alveolar function and morphology were examined. Lipase (2.5-20 micrograms/ml) adversely effected the phagocytic function of rat pulmonary alveolar macrophages in a dose-dependent manner. The lipase itself was not directly cytotoxic to these cells. Alveolar macrophages, in the absence of lipase, phagocytosed c. 35% of a given population of opsonised P. cepacia in 30 min when the ratio of bacteria:phagocyte was 10:1. Phagocytosis of P. cepacia by rat pulmonary alveolar macrophages was significantly reduced when the cells were either pre-incubated with the lipase or when phagocytosis occurred in the presence of the lipase. This was confirmed by transmission electronmicroscopy. These functional changes were associated with marked alterations of the macrophage morphology. Scanning electronmicroscopy showed that macrophages exposed to the P. cepacia lipase had fewer specialised surface structures and did not spread on plastic surfaces as well as untreated macrophages. The effects of the lipase were lost after heat inactivation, which indicates that the effects of the P. cepacia lipase were due to its enzymic activity. These results suggest that, if sufficient quantities of the enzyme are produced in vivo, lipase may be an important virulence factor for P. cepacia, allowing the organism to evade phagocytic cells.