Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice.
BACKGROUND
Surfactant protein D (SP-D) deficient mice develop emphysema-like pathology associated with focal accumulations of foamy alveolar macrophages, an excess of surfactant phospholipids in the alveolar space and both hypertrophy and hyperplasia of alveolar type II cells. These findings are associated with a chronic inflammatory state. Treatment of SP-D deficient mice with a truncated recombinant fragment of human SP-D (rfhSP-D) has been shown to decrease the lipidosis and alveolar macrophage accumulation as well as production of proinflammatory chemokines. The aim of this study was to investigate if rfhSP-D treatment reduces the structural abnormalities in parenchymal architecture and type II cells characteristic of SP-D deficiency.


METHODS
SP-D knock-out mice, aged 3 weeks, 6 weeks and 9 weeks were treated with rfhSP-D for 9, 6 and 3 weeks, respectively. All mice were sacrificed at age 12 weeks and compared to both PBS treated SP-D deficient and wild-type groups. Lung structure was quantified by design-based stereology at the light and electron microscopic level. Emphasis was put on quantification of emphysema, type II cell changes and intracellular surfactant. Data were analysed with two sided non-parametric Mann-Whitney U-test.


RESULTS
After 3 weeks of treatment, alveolar number was higher and mean alveolar size was smaller compared to saline-treated SP-D knock-out controls. There was no significant difference concerning these indices of pulmonary emphysema within rfhSP-D treated groups. Type II cell number and size were smaller as a consequence of treatment. The total volume of lamellar bodies per type II cell and per lung was smaller after 6 weeks of treatment.


CONCLUSIONS
Treatment of SP-D deficient mice with rfhSP-D leads to a reduction in the degree of emphysema and a correction of type II cell hyperplasia and hypertrophy. This supports the concept that rfhSP-D might become a therapeutic option in diseases that are characterized by decreased SP-D levels in the lung.
Knudsen
Lars
L
Department of Anatomy, Division of Electron Microscopy, University of Göttingen, Göttingen, Germany. lars.knudsen@insel.ch
Ochs
Matthias
M
Mackay
Rosemarie
R
Townsend
Paul
P
Deb
Roona
R
Mühlfeld
Christian
C
Richter
Joachim
J
Gilbert
Fabian
F
Hawgood
Samuel
S
Reid
Kenneth
K
Clark
Howard
H
D000818:Animals; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D011656:Pulmonary Emphysema / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency / Q000235:genetics* / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017384:Sequence Deletion / Q000235:genetics*
D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins