Surfactant metabolism in SP-D gene-targeted mice

Abstract

Mice with surfactant protein (SP)-D deficiency have three to four times more surfactant lipids in air spaces and lung tissue than control mice. We measured multiple aspects of surfactant metabolism and function to identify abnormalities resulting from SP-D deficiency. Relative to saturated phosphatidylcholine (Sat PC), SP-A and SP-C were decreased in the alveolar surfactant and the large-aggregate surfactant fraction. Although large-aggregate surfactant from SP-D gene-targeted [(-/-)] mice converted to small-aggregate surfactant more rapidly, surface tension values were comparable to values for surfactant from SP-D wild-type [(+/+)] mice. (125)I-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 [(3)H]palmitic acid and [(14)C]choline into Sat PC were similar, the labeled Sat PC was lost from the lungs of SP-D(+/+) mice more rapidly than from SP-D(-/-) mice. Clearance rates of intratracheal [(3)H]dipalmitoylphosphatidylcholine were used to estimate 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. SP-D deficiency results in multiple abnormalities in surfactant forms and metabolism that cannot be attributed to a single mechanism.

Pneumonitis and Emphysema in sp-C Gene Targeted Mice

“…The spots were visualized with iodine vapor, scraped, and assayed for phosphorus content. Surfactant proteins in BALF were analyzed by Western blot after SDS-PAGE (11,18).…”

Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial‐associated lymphoid tissue

“…[9][10][11] Studies with SP-D knockout mice have also indicated a role of SP-D in the regulation of surfactant lipid homeostasis. 12 Furthermore, Brinker and colleagues 13 found that human SP-D binds to immature bone marrow-derived dendritic cells (DC) in vitro in a dose-, carbohydrate-and calcium-dependent manner, enhancing the phagocytic uptake of Escherichia coli and the antigen presentation to T cells.…”

Design‐based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice

“…SP-D single deficient mice show altered lung pathology consistent with emphysema, abnormalities of alveolar macrophages, as well as of type II cells and an increased alveolar surfactant pool size (Botas et al, 1998;Ikegami et al, 2000a;Wert et al, 2000). SP-A single deficient mice lack tubular myelin but have no obvious changes in surfactant metabolism under resting conditions (Korfhagen et al, 1996;Ikegami et al, 1997).…”