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

Abstract

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.

A Recombinant Fragment of Human Surfactant Protein D Lacking the Short Collagen‐Like Stalk Fails to Correct Morphological Alterations in Lungs of SP‐D Deficient Mice

“…As c1rfhSP-D used in previous studies includes only a short collagen-like stalk and not the entire collagen-like domain (Fig. 1C), there were controversial observations between and Knudsen et al (2007). This discrepancy led us to hypothesize that the short collagen-like stalk of c1rfhSP-D might suffice to maintain the protein's biological activity.…”

“…1A) has been successfully applied in models with acute lung injury (Ikegami et al, , 2007. Regarding the SP-D knock-out mouse model, we have previously demonstrated that a recombinant fragment of human SP-D expressed in E. coli (c1rfhSP-D) exhibited antiinflammatory properties and corrected pulmonary emphysema, hyperplasia of type II cells as well as disturbances of the intracellular surfactant pool Knudsen et al, 2007). Recently, reported that the entire collagen-like domain of this protein is important for correcting some of the pulmonary abnormalities including pulmonary emphysema and disturbed intraalveolar surfactant homeostasis in the SP-D deficient mice by expressing a rat SP-D collagen deletion mutant protein lacking the entire collagen-like domain (Fig.…”

“…The data were compared with a wild-type group (WT), a PBS treated SP-D knock-out group (D2/2), and a SP-D knock-out group treated from third week to twelfth week with c1rfhSP-D (group C1) (taken from Knudsen et al, 2007). The animals investigated in the present study, including the comparison groups, were part of the same randomization process, i.e., they were from the same batch, housed at the same time under the same conditions and received the same food.…”

“…They are described in detail elsewhere (Knudsen et al, 2007). Briefly, on light microscopic level we evaluated the pulmonary emphysema quantitatively by determining the alveolar number (Sterio, 1984), the mean type II cell volume [ v N (typeII)] was estimated applying the rotator (Vedel-Jensen and Gundersen, 1985).…”

“…Fixation, sampling, and processing were carried out as described in detail elsewhere (Ochs, 2006;Knudsen et al, 2007;Mü hlfeld et al, 2007). All mice were sacrificed at age 12 weeks and fixed by instillation with a mixture of 1.5% glutaraldehyde/1.5% formaldehyde (from freshly depolymerized paraformaldehyde) in 0.15 M Hepes buffer.…”