Alveolar surfactant protein D content modulates bleomycin-induced lung injury.
BACKGROUND
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.


OBJECTIVE
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.


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.
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania School of Medicine, and Division of Neonatology, Children's Hospital of Philadelphia 19104, USA.
John
J
Casey
Jennifer
J
Kaplan
Elena N
EN
Atochina-Vasserman
Andrew J
AJ
Gow
Helchem
H
Kadire
Yaniv
Y
Tomer
James H
JH
Fisher
Samuel
S
Hawgood
Rashmin C
RC
Savani
Michael F
MF
Beers
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011650:Pulmonary Alveoli / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000502:physiology*
D037663:Pulmonary Surfactant-Associated Protein D; D001761:Bleomycin