Surfactant protein-D, a mediator of innate lung immunity, alters the products of nitric oxide metabolism.
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.
Atochina
Elena N
EN
Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, USA.
Beers
Michael F
MF
Hawgood
Samuel
S
Poulain
Francis
F
Davis
Christiana
C
Fusaro
Trevor
T
Gow
Andrew J
AJ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D005260:Female; D006720:Homozygote; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010743:Phospholipids / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000502:physiology*; D011663:Pulmonary Surfactants / Q000378:metabolism; D026403:S-Nitrosothiols / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D010743:Phospholipids; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse