SP-D-deficient mice are resistant to hyperoxia.
Surfactant protein D (SP-D), a member of the collectin superfamily, modulates pulmonary inflammatory responses and innate immunity. Disruption of the SP-D gene in mice induces peribronchiolar inflammation, accumulation of large, foamy macrophages, increased bronchoalveolar lavage (BAL) phospholipid, and pulmonary emphysema. We hypothesized that absence of SP-D aggravates hyperoxia-induced injury. To test this, SP-D-deficient (SP-D-/-) and wild-type (SP-D+/+) mice were exposed to 80% or 21% oxygen. Paradoxically, during 14 days of hyperoxia, SP-D-/- mice had 100% survival vs. 30% in SP-D+/+. The survival advantage in SP-D-/- mice was accompanied by lower histopathological injury scores at days 5 and 14, although total BAL cells (8.2 +/- 1.4 x 10(5) in SP-D-/- vs. 4.04 +/- 0.25 x 10(5) in SP-D+/+ mice) and neutrophils (1.2 +/- 0.4 x 10(5) vs. 0.03 +/- 0.02 x 10(5) in SP-D-/- and SP-D+/+, respectively) were increased. In addition, BAL protein and lung-to-body weight ratios were similarly elevated in both groups after 3, 5, and 14 days of continuous exposure. Biochemically, in contrast to SP-D+/+, SP-D-/- mice had higher levels of surfactant phospholipid and SP-B at baseline and 5 days after hyperoxia accompanied by a preservation of surfactant biophysical activity. From a multiplex assay of nine cytokines, we found elevated levels of IL-13 in BAL fluid of normoxic SP-D-/- mice compared with SP-D+/+. We conclude that the resistance of SP-D-deficient mice to hyperoxia reflects homeostatic changes in the SP-D-/- phenotype involving both phospholipid and SP-B-mediated induced resistance of surfactant to inactivation as well as changes in the immunomodulatory BAL cytokine profile.
Jain
Deepika
D
Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Room H410F, Hill Pavilion, 380 South University Ave., Philadelphia, PA 19107, USA.
Atochina-Vasserman
Elena
E
Kadire
Helchem
H
Tomer
Yaniv
Y
Inch
Adam
A
Scott
Pamela
P
Savani
Rashmin C
RC
Gow
Andrew J
AJ
Beers
Michael F
MF
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000032:analysis; D018496:Hyperoxia / Q000503:physiopathology / Q000517:prevention & control*; D018793:Interleukin-13 / Q000096:biosynthesis; D008171:Lung Diseases / Q000517:prevention & control*; D016676:Macrophages, Alveolar / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency* / Q000502:physiology
D016207:Cytokines; D018793:Interleukin-13; D037663:Pulmonary Surfactant-Associated Protein D; D009569:Nitric Oxide