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Interactions of Surfactant Protein D with Fatty Acids

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri; and Department of Human Microbiology, Tel Aviv University, Tel Aviv, Israel

Address correspondence to: Erika C. Crouch, M.D., Ph.D., Dept. of Pathology and Immunology, Barnes-Jewish Hospital, North campus, Box 8118 216 S. Kingshighway, St. Louis, MO 63110. E-mail: crouch{at}path.wustl.edu

Surfactant Protein D (SP-D) plays important roles in antimicrobial host defense, inflammatory and immune regulation, and pulmonary surfactant homeostasis. The best-characterized endogenous ligand is phosphatidylinositol; however, this lipid interaction at least in part involves the carbohydrate moiety. In this study we observed that SP-D binds specifically to saturated, unsaturated, and hydroxylated fatty acids (FA). Binding of biotinylated-SP-D to FAs or biotinylated FA to SP-D was dose-dependent, saturable, and specifically competed by the corresponding unlabeled probe. Specific binding to FA chains was also demonstrated by solution phase competition for FA binding to acrylodan-labeled FA binding protein (ADIFAB), and by overlay of thin layer chromatograms with SP-D. Maximal binding to FA was dependent on calcium, and binding was localized to the neck and carbohydrate recognition domains (CRD) using recombinant trimeric neck+CRDs. Saccharide ligands showed complex, dose-dependent effects on FA binding, and FAs showed dose- and physical state–dependent effects on the binding of SP-D to mannan. In addition, CD spectroscopy suggested alterations in SP-D structure associated with binding to monomeric FA. Together, the findings indicate specific binding of FA to one or more sites in the CRD. We speculate that the binding of SP-D to the fatty acyl chains of surfactant lipids, microbial ligands, or other complex lipids contributes to the diverse biological functions of SP-D in vivo.

Abbreviations: acrylodan-labeled fatty acid binding protein, ADIFAB • bovine serum albumin, BSA • circular dichroism, CD • critical micellar concentration, CMC • carbohydrate recognition domain, CRD • dimethylsulfoxide, DMSO • fatty acid, FA • fatty acid–free BSA, FAF-BSA • Hepes-buffered saline, HBS • molecular weight cutoff, MWCO • phosphate-buffered saline, PBS • phosphatidylinositol, PI • recombinant rat surfactant protein D, RrSP-D • surfactant protein A, SP-A • surfactant protein D, SP-D • sub-micellar, sub-CMC

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