Surfactant protein-D and pulmonary host defense

Surfactant protein-D (SP-D) participates in the innate response to inhaled Microorganisms and organic Antigens, and contributes to immune and inflammatory regulation within the lung. SP-D is synthesized and secreted by alveolar and bronchiolar epithelial cells, but is also expressed by epithelial cells lining various exocrine ducts and the mucosa of the gastrointestinal and genitourinary tracts. SP-D, a collagenous calcium-dependent lectin (or collectin), binds to surface glycoconjugates expressed by a wide variety of Microorganisms, and to Oligosaccharides associated with the surface of various complex organic Antigens. SP-D also specifically interacts with glycoconjugates and other molecules expressed on the surface of Macrophages, neutrophils, and lymphocytes. In addition, SP-D binds to specific surfactant-associated Lipids and can influence the organization of lipid mixtures containing phosphatidylinositol in vitro. Consistent with these diverse in vitro activities is the observation that SP-D-deficient transgenic mice show abnormal accumulations of surfactant Lipids, and respond abnormally to challenge with respiratory viruses and bacterial Lipopolysaccharides. The phenotype of Macrophages isolated from the Lungs of SP-D-deficient mice is altered, and there is circumstantial evidence that abnormal oxidant metabolism and/or increased metalloproteinase expression contributes to the development of Emphysema. The expression of SP-D is increased in response to many forms of lung injury, and deficient accumulation of appropriately oligomerized SP-D might contribute to the pathogenesis of a variety of human lung diseases.