REGULATION AND FUNCTION OF SP-D

University Of Colorado Denver, Aurora CO

Investigators

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Abstract

DESCRIPTION: Surfactant protein-D is a recently described member of the collectin family. As a family, the collectins are important pattern recognition molecules that bind microbial carbohydrates in a calcium dependent manner. Several mechanisms of enhanced microbial clearance have been demonstrated with members of this family of molecules. SP-D is expressed in alveolar epithelium and gastric mucosa in cells that are important in maintaining a phospholipid barrier to the environment. SP-D binds and agglutinates a variety of enteric and respiratory pathogens including influenza A virus, Salmonella minnesota, Escherichia coli, Cryptococcus neoformans, and Pneumocystis carinii at physiologically relevant concentrations. As a consequence of binding, several such organisms become adherent to alveolar macrophages but are not opsonized. Alveolar macrophages bind SP-D by two distinct mechanisms and SP-D is a potent chemotactic agent for both monocytes and neutrophils. in vitro experiments suggest that SP-D is an important host defense molecule for Influenza A viruses and may have a role in preventing secondary bacterial infections after influenza infection. However, a role for SP-D has not been demonstrated in vivo. It is hypothesized that SP-D has a role in regulating surfactant secretion. Since SP-D is chemotactic, SP-D may regulate the abundance of alveolar macrophages. The investigators further hypothesize that SP-D promotes clearance of respiratory pathogens in vivo and that increasing alveolar SP-D may increase resistance to specific pathogens. They propose to construct transgenic mice which carry null mutations for SP-D and to use an existing colony of mice which overexpress SP-D to test those hypotheses. They will study the mechanisms underlying these functions. Such investigations offer opportunities to better understand host resistance. A better understanding of innate immunity offers opportunities to identify individuals at risk for specific respiratory infections and to develop new therapeutic strategies.