Alveolar surfactant protein D content modulates bleomycin-induced lung injury

John Casey, Jennifer Kaplan, Elena N. Atochina-Vasserman, Andrew J. Gow, Helchem Kadire, Yaniv Tomer, James H. Fisher, Samuel Hawgood, Rashmin C. Savani, Michael F. Beers

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Rationale: Surfactant protein D (SP-D) is a collectin family member with demonstrated immunomodulatory properties in vitro. We hypothesized that SP-D modulates inflammation during noninfectious lung injury in vivo. Objectives: To investigate the association of alveolar SP-D and injury, we studied the responses of transgenic mice expressing varying levels of SP-D to intratracheal bleomycin (ITB). Methods: Eight-week old C57/BL6 SP-D-deficient (-/-) mice and syngeneic wild-type (WT) controls or Swiss Black SP-D-overexpressing (SP-D OE) mice and littermate controls received either ITB or saline and were followed for up to 21 d. Measurements and Results: Kaplan-Meier analysis demonstrated a dose-dependent decrease in survival in ITB SP-D (-/-) mice receiving 2 U/kg bleomycin, with a 14-d mortality of 100% versus 0% mortality for WT receiving 2 U/kg ITB or SP-D (-/-) mice given saline (p < 0.05). At 8 d, ITB SP-D (-/-) mice had greater respiratory distress (frequency/tidal volume) and weight loss than ITB WT mice. Furthermore, bronchoalveolar lavage cellularity, pulmonary parenchymal inflammation, and tissue 3-nitrotyrosine (NO2 Y) were increased to a greater extent in ITB SP-D (-/-) mice. By 21 d, compared with all groups, ITB SP-D (-/-) survivors had increased Trichrome staining and tissue hydroxyproline levels. As proof of principle, SP-D OE mice were highly resistant to bleomycin-induced morbidity and mortality at doses up to 3 U/kg. Conclusions: These data provide new in vivo evidence for an antiinflammatory role for SP-D in response to noninfectious, subacute lung injury via modulation of oxidative-nitrative stress.

Original languageEnglish (US)
Pages (from-to)869-877
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume172
Issue number7
DOIs
StatePublished - Oct 1 2005

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Pulmonary Surfactant-Associated Protein D
Bleomycin
Lung Injury
Mortality
Collectins
Hydroxyproline
Tidal Volume
Kaplan-Meier Estimate
Bronchoalveolar Lavage

Keywords

  • Bleomycin
  • Collectins
  • Innate immunity
  • Lung
  • Nitric oxide

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Casey, J., Kaplan, J., Atochina-Vasserman, E. N., Gow, A. J., Kadire, H., Tomer, Y., ... Beers, M. F. (2005). Alveolar surfactant protein D content modulates bleomycin-induced lung injury. American Journal of Respiratory and Critical Care Medicine, 172(7), 869-877. https://doi.org/10.1164/rccm.200505-767OC

Alveolar surfactant protein D content modulates bleomycin-induced lung injury. / Casey, John; Kaplan, Jennifer; Atochina-Vasserman, Elena N.; Gow, Andrew J.; Kadire, Helchem; Tomer, Yaniv; Fisher, James H.; Hawgood, Samuel; Savani, Rashmin C.; Beers, Michael F.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 172, No. 7, 01.10.2005, p. 869-877.

Research output: Contribution to journalArticle

Casey, J, Kaplan, J, Atochina-Vasserman, EN, Gow, AJ, Kadire, H, Tomer, Y, Fisher, JH, Hawgood, S, Savani, RC & Beers, MF 2005, 'Alveolar surfactant protein D content modulates bleomycin-induced lung injury', American Journal of Respiratory and Critical Care Medicine, vol. 172, no. 7, pp. 869-877. https://doi.org/10.1164/rccm.200505-767OC
Casey, John ; Kaplan, Jennifer ; Atochina-Vasserman, Elena N. ; Gow, Andrew J. ; Kadire, Helchem ; Tomer, Yaniv ; Fisher, James H. ; Hawgood, Samuel ; Savani, Rashmin C. ; Beers, Michael F. / Alveolar surfactant protein D content modulates bleomycin-induced lung injury. In: American Journal of Respiratory and Critical Care Medicine. 2005 ; Vol. 172, No. 7. pp. 869-877.
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abstract = "Rationale: Surfactant protein D (SP-D) is a collectin family member with demonstrated immunomodulatory properties in vitro. We hypothesized that SP-D modulates inflammation during noninfectious lung injury in vivo. Objectives: To investigate the association of alveolar SP-D and injury, we studied the responses of transgenic mice expressing varying levels of SP-D to intratracheal bleomycin (ITB). Methods: Eight-week old C57/BL6 SP-D-deficient (-/-) mice and syngeneic wild-type (WT) controls or Swiss Black SP-D-overexpressing (SP-D OE) mice and littermate controls received either ITB or saline and were followed for up to 21 d. Measurements and Results: Kaplan-Meier analysis demonstrated a dose-dependent decrease in survival in ITB SP-D (-/-) mice receiving 2 U/kg bleomycin, with a 14-d mortality of 100{\%} versus 0{\%} mortality for WT receiving 2 U/kg ITB or SP-D (-/-) mice given saline (p < 0.05). At 8 d, ITB SP-D (-/-) mice had greater respiratory distress (frequency/tidal volume) and weight loss than ITB WT mice. Furthermore, bronchoalveolar lavage cellularity, pulmonary parenchymal inflammation, and tissue 3-nitrotyrosine (NO2 Y) were increased to a greater extent in ITB SP-D (-/-) mice. By 21 d, compared with all groups, ITB SP-D (-/-) survivors had increased Trichrome staining and tissue hydroxyproline levels. As proof of principle, SP-D OE mice were highly resistant to bleomycin-induced morbidity and mortality at doses up to 3 U/kg. Conclusions: These data provide new in vivo evidence for an antiinflammatory role for SP-D in response to noninfectious, subacute lung injury via modulation of oxidative-nitrative stress.",
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