Surfactant protein-A enhances ureaplasmacidal activity in vitro

BACKGROUND: Persistent respiratory tract colonization with Ureaplasma spp. in preterm infants is a significant risk factor for the development of the chronic lung disorder, bronchopulmonary dysplasia (BPD). Surfactant protein-A (SP-A), a lung collectin critical for bacterial clearance and regulating inflammation, is deficient in the preterm lung. In an experimental Ureaplasma-pneumonia model, infected SP-A deficient mice exhibited delayed bacterial clearance and an exaggerated inflammatory response compared to infected wild-type mice. The objective was to analyze the role of SP-A in Ureaplasma clearance in vitro. SUBJECTS AND METHODS: We analyzed SP-A binding to Ureaplasma isolates and SP-A-mediated ureaplasmal phagocytosis and killing by cultured RAW 264.7 macrophages. RESULTS: Calcium-dependent SP-A binding was similar among Ureaplasma isolates tested. Pre-incubation of RAW 264.7 cells with SP-A (10-50 μg/ml) enhanced phagocytosis of fluorescein-isothiocyanate (FITC)-labeled Ureaplasma. Surfactant protein-A also increased ureaplasmacidal activity of RAW 264.7 cells by 2.1-fold over 4 h. Pre-incubation of RAW 264.7 cells with 10 μg/ml SP-A reduced lipopolysaccharide (LPS) (100 ng/ml) and Ureaplasma (10(6) color changing units/ml)-stimulated release of tumor necrosis factor-α (TNF-α) by 46% and 43%, respectively, but did not affect transforming growth factor β(1) (TGFβ(1)) release. CONCLUSIONS: These in vitro data confirm that SP-A is important in host defense to perinatally-acquired Ureaplasma infection.