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 language | English |
|---|---|
| Pages (from-to) | 869-877 |
| Number of pages | 9 |
| Journal | American Journal of Respiratory and Critical Care Medicine |
| Volume | 172 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 1 Oct 2005 |
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Keywords
- Bleomycin
- Collectins
- Innate immunity
- Lung
- Nitric oxide
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - Alveolar surfactant protein D content modulates bleomycin-induced lung injury
AU - Casey, John
AU - Kaplan, Jennifer
AU - Atochina-Vasserman, Elena N.
AU - Gow, Andrew J.
AU - Kadire, Helchem
AU - Tomer, Yaniv
AU - Fisher, James H.
AU - Hawgood, Samuel
AU - Savani, Rashmin C.
AU - Beers, Michael F.
PY - 2005/10/1
Y1 - 2005/10/1
N2 - 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.
AB - 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.
KW - Bleomycin
KW - Collectins
KW - Innate immunity
KW - Lung
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=25444501761&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25444501761&partnerID=8YFLogxK
U2 - 10.1164/rccm.200505-767OC
DO - 10.1164/rccm.200505-767OC
M3 - Article
C2 - 15994463
AN - SCOPUS:25444501761
VL - 172
SP - 869
EP - 877
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 7
ER -