Surfactant metabolism in SP-D gene-targeted mice

Mice with surfactant protein (SP)-D deficiency have three to four times mor e surfactant lipids in air spaces and lung tissue than control mice. We mea sured multiple aspects of surfactant metabolism and function to identify ab normalities resulting from SP-D deficiency. Relative to saturated phosphati dylcholine (Sat PC), SP-A and SP-C were decreased in the alveolar surfactan t and the large-aggregate surfactant fraction. Although large-aggregate sur factant from SP-D gene-targeted [(-/-)] mice converted to small-aggregate s urfactant more rapidly, surface tension values were comparable to values fo r surfactant from SP-D wild-type [(-/-)] mice. I-125-SP-D was cleared with a half-life of 7 h from SP-D(-/-) mice vs. 13 h in SP-D(+/+) mice. Although initial incorporation and secretion rates for [H-3] palmitic acid and [C-1 4] choline into Sat PC were similar, the labeled Sat PC was lost from the l ungs of SP-D(+/+) mice more rapidly than from SP-D(+/+) mice. Clearance rat es of intratracheal [H-3] dipalmitoylphosphatidylcholine were used to estim ate net clearances of Sat PC, which were approximately threefold higher for alveolar and total lung Sat PC in SP-D(-/-) mice than in SP-D(+/+) mice. S P-D deficiency results in multiple abnormalities in surfactant forms and me tabolism that cannot be attributed to a single mechanism.