Identification and Characterization of a Novel Interaction between Pulmonary Surfactant Protein D and Decorin

Abstract

Surfactant-associated protein D (SP-D) is a collectin Surfactant protein D (SP-D),1 a C-type lectin, is present in pulmonary surfactant and several other mucosal surfaces (1). Recent studies show that SP-D modulates multiple functions: innate immunity (2, 3), allergic response (4), expression of matrix metalloproteases (5, 6), alveolar wall remodeling-emphysema, fibrosis, and lipid and macrophage homeostasis (7-9). Taken together, these results indicate that SP-D regulates pathway(s) that involve matrix-related proteins. However, the SP-D-binding proteins, which may participate in this pathway, are not known.In the lung, pulmonary type II cells express and secrete SP-D into the alveolar environment (1, 10). SP-D expression is developmentally regulated, and its concentration increases in amniotic fluid during the last few weeks of pregnancy (10). In adult lungs, the concentration of SP-D varies significantly during allergic and pathological conditions, and therapeutic lung washings and amniotic fluid are routinely used for the purification of SP-D (11-13). Purified SP-D is a glycoprotein and is composed of a short interchain disulfide bond-forming N-terminal domain, a collagen-like region with Gly-X-Y repeats (where X represents any amino acid and Y is often hydroxyproline or hydroxylysine), a hydrophobic neck region, and a Cterminal globular carbohydrate recognition domain (CRD) (14 -16). Three CRDs are held together by protein-protein interactions at the hydrophobic neck region (17). The collagenlike region folds into a ϳ45-nm-long triple helix, and the chains are tethered at the end via the N-terminal segment. Trimeric SP-D subunits (3 ϫ 43 kDa) further assemble as higher order oligomers via interactions at the collagen-like and N-terminal domains. Dodecameric SP-D are X-shaped ϳ100-nm-long molecules (516 kDa), whereas higher order multimers appear as "fuzzy balls" (16,18). CRDs of SP-D can interact with glycoproteins (19), carbohydrates (20 -22), and lipids (23) present on microbial surfaces, phosphatidylinositol component of pulmonary surfactant lipid (24), and receptors/binding proteins such as CD14 (25) and gp-340 (26). N-terminal (27) and collagen-like (14) regions of SP-D are glycosylated and are implicated in structural organization and receptor binding. The N-terminal domain is important for disulfide-dependent oligomerization (28), and X-like structural assembly (29). Microfibril-associated protein 4, a fibrinogen-like domain-containing protein with lectin activity, binds to the collagen-like region of SP-D (30); however, its biological function is not clearly established.

Major House Dust Mite Allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 Degrade and Inactivate Lung Surfactant Proteins A and D

“…Surface Plasmon Resonance-Biotinylated Der p 1, Der f 1, and mannan were immobilized on streptavidin-coated BIAcore chips as described previously (39). 60 g/ml NhSP-D or 120 g/ml rfhSP-D had been incubated with 1.25 g/ml enzymatically active Der p 1 and Der f 1 for 20 h in 10 mM HEPES, 150 mM NaCl, 5 mM CaCl 2 (HSC) in the presence or absence of 10 mM IAA were flowed over the cells in HSC, 0.05% (v/v) surfactant P20.…”

Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

“…SP-D could also contribute to adaptive immune responses through facilitating presentation of Ag by dendritic cells (20) and decreasing lymphocyte activation and proliferation (21). SP-D has also been shown to bind to a select few host molecules including scavenger receptor rich gp340, microfibrilassociated protein 4, decorin, and DNA (22)(23)(24)(25)(26). gp340 has significant anti-influenza activity in its own right (27).…”

Innate Immune Collectin Surfactant Protein D Simultaneously Binds Both Neutrophil Extracellular Traps and Carbohydrate Ligands and Promotes Bacterial Trapping

“…Human SP-D from bronchoalveolar lavage (BAL) fluid of a patient with alveolar proteinosis was purified as previously described (24,(31)(32)(33).…”