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

Knudsen, Lars; Wucherpfennig, K.; Mackay, Rose-Marie; Paul, Thierry; Mühlfeld, Christian; Richter, Joachim; Hawgood, Samuel; Clark, Howard; Ochs, Matthias

doi:10.1002/ar.20830

Cited by 22 publications

(17 citation statements)

References 44 publications

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“…However, a fragment without the collagen-like tail does not display these therapeutic effects, pointing to an important role of the collagen-like domain for the protein’s function (Kingma et al, 2006; Knudsen et al, 2009). Human lung diseases characterised by chronic inflammation and low levels of SP-D in BAL include cystic fibrosis (in particular during acute exacerbation) (Postle et al, 1999; Noah et al, 2003) and smoke-related COPD (Honda et al, 1996; Betsuyaku et al, 2004).…”

Section: The Role Of Sp-a and Sp-d In The Healthy Lung – Lessons Lmentioning

confidence: 99%

Recent advances in alveolar biology: Evolution and function of alveolar proteins

Orgeig

Hiemstra

Veldhuizen

et al. 2010

Respiratory Physiology & Neurobiology

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This review is focused on the evolution and function of alveolar proteins. The lung faces physical and environmental challenges, due to changing pressures/volumes and foreign pathogens, respectively. The pulmonary surfactant system is integral in protecting the lung from these challenges via two groups of surfactant proteins – the small molecular weight hydrophobic SPs, SP-B and -C, that regulate interfacial adsorption of the lipids, and the large hydrophilic SPs, SP-A and -D, which are surfactant collectins capable of inhibiting foreign pathogens. Further aiding pulmonary host defence are non-surfactant collectins and antimicrobial peptides that are expressed across the biological kingdoms. Linking to the first symposium session, which emphasised molecular structure and biophysical function of surfactant lipids and proteins, this review begins with a discussion of the role of temperature and hydrostatic pressure in shaping the evolution of SP-C in mammals. Transitioning to the role of the alveolus in innate host defence we discuss the structure, function and regulation of antimicrobial peptides, the defensins and cathelicidins. We describe the recent discovery of novel avian collectins and provide evidence for their role in preventing influenza infection. This is followed by discussions of the roles of SP-A and SP-D in mediating host defence at the alveolar surface and in mediating inflammation and the allergic response of the airways. Finally we discuss the use of animal models of lung disease including knockouts to develop an understanding of the role of these proteins in initiating and/or perpetuating disease with the aim of developing new therapeutic strategies.

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Section: The Role Of Sp-a and Sp-d In The Healthy Lung – Lessons Lmentioning

confidence: 99%

Recent advances in alveolar biology: Evolution and function of alveolar proteins

Orgeig

Hiemstra

Veldhuizen

et al. 2010

Respiratory Physiology & Neurobiology

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“…Indeed, intranasal treatment of SP-D deficient mice with a recombinant fragment of human SP-D (rfhSP-D) containing a short stalk of the collagen-like domain is able to largely prevent the emphysema-like alterations as well as those of type II cells and lamellar bodies [105]. However, treatment with rfhSP-D without the short stalk of the collagen-like domain fails to do so [106], suggesting that this part of the protein, most likely by assembling three monomer fragments to form a homotrimer, is essential for its proper biological function. The therapeutic potential of rfhSP-D containing the short stalk therefore deserves further evaluation.…”

Section: Phenotype Analysis Of Lung Collectin Deficient Micementioning

confidence: 99%

The Closer we Look the more we See? Quantitative Microscopic Analysis of the Pulmonary Surfactant System

Ochs

2010

Cell Physiol Biochem

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The surfactant system of the lung has essential biophysical and immunomodulatory functions. Only at the electron microscopic level does surfactant reveal its morphological complexity - and beauty. Therefore, morphological tools are indispensible to characterize the surfactant system in health and disease. Stereology provides the gold standard for obtaining quantitative (morphometric) data in microscopy. The combination of microscopy and stereology allows for qualitative and quantitative analysis of the intraalveolar as well as the intracellular surfactant pool, both in its preserved microorganization and localization within the lung. Surfactant-producing alveolar epithelial type II cells can be counted and sampled for size estimation with physical disectors at a high magnification light microscopic level. The number of their surfactant storing lamellar bodies can be estimated using physical disectors at the electron microscopic level. Electron tomography allows for high resolution 3D visualization of lamellar body fusion pores. Intraalveolar surfactant subtypes can be quantitated in situ, thus reflecting the functional state of the intraalveolar surfactant pool. By immunoelectron microscopy, surfactant protein distribution can be analyzed. These methods allow for a comprehensive quantitative analysis of surfactant (ultra-)structure. Here, we give an overview on the analysis of the normal and disordered surfactant system by electron microscopy and stereology.

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“…Stereological parameters useful for characterizing pulmonary emphysema include the total volume of septal tissue and the total surface area of alveolar epithelium [48][49][50][51]. These parameters can be obtained by point and intersection counting using thin sections.…”

Section: Sampling and Further Processing Of Lung Tissuementioning

confidence: 99%

Microscopy-based quantitative analysis of lung structure: application in diagnosis

Knudsen¹,

Ochs²

2011

Expert Opinion on Medical Diagnostics

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In view of the recently published standards for quantitative assessment of lung structure, unbiased stereological methods are strongly recommended, particularly as they provide valuable information in diagnosing lung diseases and allow a statistically valid quantitative comparison between different groups. Future developments will make the application of stereology in lung biology and pathology even more efficient. Moreover, there is also the potential for combing the principles of stereology with other imaging modalities (e.g., radiological), which will allow for non-invasive lung stereology.

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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

Cited by 22 publications

References 44 publications

Recent advances in alveolar biology: Evolution and function of alveolar proteins

Recent advances in alveolar biology: Evolution and function of alveolar proteins

The Closer we Look the more we See? Quantitative Microscopic Analysis of the Pulmonary Surfactant System

Microscopy-based quantitative analysis of lung structure: application in diagnosis

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