Surfactant protein-D, a mediator of innate lung immunity, alters the products of nitric oxide metabolism

Am J Respir Cell Mol Biol. 2004 Mar;30(3):271-9. doi: 10.1165/rcmb.2003-0091OC. Epub 2003 Jul 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cell Count
  • Female
  • Homozygote
  • Immunity, Innate*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Phospholipids / metabolism
  • Pneumonia / immunology
  • Pneumonia / metabolism*
  • Pulmonary Surfactant-Associated Protein D / genetics
  • Pulmonary Surfactant-Associated Protein D / physiology*
  • Pulmonary Surfactants / metabolism
  • S-Nitrosothiols / metabolism
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism

Substances

  • Phospholipids
  • Pulmonary Surfactant-Associated Protein D
  • Pulmonary Surfactants
  • S-Nitrosothiols
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse