251. Surfactant protein-D, a mediator of innate lung immunity, alters the products of nitric oxide metabolism.
- Author
-
Atochina EN, Beers MF, Hawgood S, Poulain F, Davis C, Fusaro T, and Gow AJ
- Subjects
- Animals, Bronchoalveolar Lavage Fluid chemistry, Cell Count, Female, Homozygote, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Nitric Oxide Synthase Type II, Phospholipids metabolism, Pneumonia immunology, Pulmonary Surfactant-Associated Protein D genetics, Pulmonary Surfactants metabolism, S-Nitrosothiols metabolism, Tyrosine metabolism, Immunity, Innate, Nitric Oxide metabolism, Nitric Oxide Synthase metabolism, Pneumonia metabolism, Pulmonary Surfactant-Associated Protein D physiology, Tyrosine analogs & derivatives
- Abstract
Surfactant protein (SP)-D, a 43-kD multifunctional collagen-like lectin, is synthesized and secreted by the airway epithelium. SP-D knockout (SP-D [-/-]) mice exhibit an increase in the number and size of airway macrophages, peribronchiolar inflammation, increases in metalloproteinase activity, and development of emphysema. Nitric oxide (NO) is involved in a variety of signaling processes, and because altered NO metabolism has been observed in inflammation, we hypothesized that alterations in its metabolism would underlie the proinflammatory state observed in SP-D deficiency. Examination of the bronchial alveolar lavage (BAL) from SP-D (-/-) mice reveals a significant increase in protein and phospholipid content and total cell count. NO production and inducible NO synthase expression were increased in the BAL; however, there was a decline in S-nitrosothiol (SNO) content in the BAL and a loss of SNO immunoreactivity within the tissue. This decline in SNO was accompanied by an increase in nitrotyrosine staining. We conclude that inflammation that occurs in SP-D deficiency results in an increase in NO production and a shift in the chemistry and targets of NO. We speculate that the proinflammatory response due to SP-D deficiency results, in part, from a disruption of NO-mediated signaling within the innate immune system.
- Published
- 2004
- Full Text
- View/download PDF