ALTERED SURFACTANT HOMEOSTASIS AND ALVEOLAR TYPE-II CELL MORPHOLOGY IN MICE LACKING SURFACTANT PROTEIN-D

Surfactant protein D (SP-D) is one of two collectins found in the pulm onary alveolus, On the basis of homology with other collectins, potent ial functions for SP-D include roles in innate immunity and surfactant metabolism, The SP-D gene was disrupted in embryonic stem cells by ho mologous recombination to generate mice deficient in SP-D, Mice hetero zygous for the mutant SP-D allele had SP-D concentrations that were ap proximately 50% wild type but no other obvious phenotypic abnormality. Mice totally deficient in SP-D were healthy to 7 months but had a pro gressive accumulation of surfactant lipids, SP-A, and SP-B in the alve olar space. By 8 weeks the alveolar phospholipid pool was 8-fold highe r than wild-type littermates. There was also a 10-fold accumulation of alveolar macrophages in the null mice, and many macrophages were both multinucleated and foamy in appearance. Type II cells in the null mic e were hyperplastic and contained giant lamellar bodies. These alterat ions in surfactant homeostasis were not associated with detectable cha nges in surfactant surface activity, postnatal respiratory function, o r survival. The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis.