Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice

Knudsen, Lars; Ochs, Matthias; Mackay, Rosemarie; Townsend, Paul; Deb, Roona; Mühlfeld, Christian; Richter, Joachim; Gilbert, Fabian; Hawgood, Samuel; Reid, Kenneth; Clark, Howard (2007). Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice. Respiratory research, 8, p. 70. London: BioMed Central 10.1186/1465-9921-8-70

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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. MAIN 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. CONCLUSION: 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy

UniBE Contributor:

Knudsen, Lars; Ochs, Matthias and Mühlfeld, Christian

ISSN:

1465-9921

ISBN:

17915009

Publisher:

BioMed Central

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:55

Last Modified:

02 Jan 2015 09:18

Publisher DOI:

10.1186/1465-9921-8-70

PubMed ID:

17915009

Web of Science ID:

000251134400001

BORIS DOI:

10.7892/boris.23540

URI:

https://boris.unibe.ch/id/eprint/23540 (FactScience: 42254)

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