Metabolism of surfactant protein (SP) A and dipalmitoylphosphatidylcholine
(DPPC) was assessed in alveolar macrophages isolated from granulocyte-macro
phage colony-stimulated factor (GM-CSF) gene-targeted [GM(2/2)] mice, wild-
type mice, and GM(2/2) mice expressing GM-CSF under control of the SP-C pro
moter element (SP-C-GM). Although binding and uptake of I-125-SP-A were sig
nificantly increased in alveolar macrophages from GM(2/2) compared with wil
d type or SP-C-GM mice, catabolism of I-125-SP-A was markedly decreased in
GM(2/2) mice. Association of [H-3] DPPC with alveolar macrophages from GM(2
/2), wild-type, and SP-C-GM mice was similar; however, catabolism of DPPC w
as markedly reduced in cells from GM(2/2) mice. Fluorescence-activated cell
sorter analysis demonstrated decreased catabolism of rhodamine-labeled dip
almitoylphosphatidylethanolamine by alveolar macrophages from GM(2/2) mice.
GM-CSF deficiency was associated with increased SP-A uptake by alveolar ma
crophages but with impaired surfactant lipid and SP-A degradation. These fi
ndings demonstrate the important role of GM-CSF in the regulation of alveol
ar macrophage lipid and SP-A catabolism.