Am. J. Respir. Cell Mol. Biol., Vol 12, No. 2, Feb 1995, 190-195.
Hyperoxic suppression of Fc-gamma receptor-mediated phagocytosis by isolated murine pulmonary macrophages
RE Crowell, G Hallin, E Heaphy and C Mold
Department of Medicine, University of New Mexico School of Medicine, albuquerque 87131.
Lower respiratory tract exposure to high oxygen (O2) concentrations is
known to induce changes in pulmonary function through effects on several
cell types located within the lung parenchyma, including pulmonary
macrophages (PM). We studied the effects of hyperoxic exposure on
phagocytosis via Fc-gamma receptors (FcR) on isolated murine PM. PM
cultured in hyperoxic conditions exhibited little change in ingestion via
FcR for up to 96 h, compared with significant increases in ingestion by PM
cultured in 21% O2 over the same time period. This suppression was
reversible and occurred whether 50 or 100% O2 concentrations were used for
hyperoxic exposure. Addition of the potent macrophage-activating agent
interferon-gamma (IFN-gamma) to cultured PM further increased FcR-mediated
phagocytosis in normoxic PM but had no effect on PM cultured in 100% O2.
Analysis of FcR expression by flow cytometry using monoclonal antibodies
specific for two different FcR classes revealed that culture in normoxic
conditions increased surface expression of both FcR classes. Hyperoxic
culture inhibited up-regulation of the high-affinity FcR but did not affect
low- affinity FcR up-regulation, suggesting that hyperoxic effects were not
due solely to effects on regulation of FcR expression. However, hyperoxic
exposure completely suppressed FcR-mediated actin polymerization. These
findings suggest that hyperoxic exposure impairs PM ability to increase
FcR-mediated phagocytic activity after appropriate stimulation, which could
impair the lung's defenses against infection.
