The Role of Homodimers in Surfactant Protein B Function in Vivo *

Surfactant protein B (SP-B) is detected in the airways as a sulfhydryl-dependent dimer (M r ∼ 16,000). To test the hypothesis that formation of homodimers is critical for SP-B function, the cysteine residue reported to be involved in SP-B dimerization was mutated to serine (Cys248 → Ser) and the mutated protein was targeted to the distal respiratory epithelium of transgenic mice. Transgenic lines which demonstrated appropriate processing, sorting, and secretion of human SP-B monomer were crossed with SP-B +/− mice to achieve expression of human monomer in the absence of endogenous SP-B dimer (hSP-Bmon, mSP-B−/−). In two of three transgenic lines, hSP-Bmon, mSP-B−/− mice had normal lung structure, complete processing of SP-C proprotein, well formed lamellar bodies, and normal longevity. Pulmonary function studies revealed an altered hysteresis curve for hSP-Bmon, mSP-B−/− mice relative to wild type mice. Large aggregate surfactant fractions from hSP-Bmon, mSP-B−/− mice resulted in higher minimum surface tension in vitro compared with surfactant from wild type mice. Surfactant lipids supplemented with 2% hSP-B monomer resulted in slower adsorption and higher surface tension than surfactant with 2% hSP-B dimer. Taken together, these data indicate a role for SP-B dimer in surface tension reduction in the alveolus.