Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient miceReportar como inadecuado




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Respiratory Research

, 8:70

First Online: 03 October 2007Received: 15 May 2007Accepted: 03 October 2007

Abstract

BackgroundSurfactant 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.

MethodsSP-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 ResultsAfter 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.

ConclusionTreatment 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.

AbbreviationsSP-Dsurfactant protein D

SP-Asurfactant protein A

rfhSP-Dtruncated fragment of human surfactant protein D

CRDcarbohydrate recognizing domain

BALbronchoalveolar lavage

Vvolume

VVvolume fraction

Ssurface area

SVsurface area density

Open image in new windowmean thickness

Nnumber

NVnumerical density

Open image in new windowNnumber-weighted mean volume

Open image in new windowVvolume-weighted mean volume

parparenchyma

airairspace

sepseptal tissue

alvepialveolar epithelium

alvalveoli

typeIItype II cells

lblamellar bodies

ROSreactive oxygen species

GM-CSFgranulocyte macrophage-colony stimulating factor

MMPmatrix metalloproteinases

COPDchronic obstructive pulmonary disease

MCP-1monocyte chemoattractant protein 1

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Autor: Lars Knudsen - Matthias Ochs - Rosemarie MacKay - Paul Townsend - Roona Deb - Christian Mühlfeld - Joachim Richter - Fabia

Fuente: https://link.springer.com/







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