Structure and properties of surfactant protein B

Hawgood, Samuel; Derrick, Matthew; Poulain, Francis R

doi:10.1016/s0925-4439(98)00064-7

Cited by 207 publications

(183 citation statements)

References 44 publications

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“…A lack of mature SP-B but not precursors of SP-B in babies with absence of lamellar bodies and the intraalveolar accumulation of precursors of SP-B in hereditary and acquired pulmonary alveolar proteinosis are associated with a severe pulmonary dysfunction. 2 The molecular mechanisms leading to a failure of normal processing of proSP-B are still obscure. A lack or deficiency of the proteases involved in the processing might be a possible explanation.…”

Section: Fig 1 Localization Of Napsin a In The Human Lung By Immunomentioning

confidence: 99%

“…2). Hereditary SP-B deficiency in infants or mice leads to respiratory failure at birth (3)(4)(5)(6).…”

mentioning

confidence: 99%

“…Furthermore, only SP-B precursors are detected in babies with congenital surfactant defects characterized by the absence of lamellar bodies in type-II pneumocytes. 2 Therefore, insufficient processing of proSP-B due to a lack or dysfunction of one or more proteases involved in SP-B processing might be yet another undiscovered cause of surfactant dysfunction in pulmonary diseases in babies, children, and adults.…”

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confidence: 99%

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Involvement of Napsin A in the C- and N-terminal Processing of Surfactant Protein B in Type-II Pneumocytes of the Human Lung

Brasch

Ochs

Kähne

et al. 2003

Journal of Biological Chemistry

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Surfactant protein B (SP-B) is a critical component of pulmonary surfactant, and a deficiency of active SP-B results in fatal respiratory failure. SP-B is synthesized by type-II pneumocytes as a 42-kDa propeptide (proSP-B), which is posttranslationally processed to an 8-kDa surface-active protein. Napsin A is an aspartic protease expressed in type-II pneumocytes. To characterize the role of napsin A in the processing of proSP-B, we colocalized napsin A and precursors of SP-B as well as SP-B in the Golgi complex, multivesicular, composite, and lamellar bodies of type-II pneumocytes in human lungs using immunogold labeling. Furthermore, we measured aspartic protease activity in isolated lamellar bodies as well as isolated human type-II pneumocytes and studied the cleavage of proSP-B by napsin A and isolated lamellar bodies in vitro. Both, napsin A and isolated lamellar bodies cleaved proSP-B and generated three identical processing products. Processing of proSP-B by isolated lamellar bodies was completely inhibited by an aspartic protease inhibitor. Sequence analysis of proSP-B processing products revealed several cleavage sites in the Nand C-terminal propeptides as well as one in the mature peptide. Two of the four processing products generated in vitro were also detected in type-II pneumocytes. In conclusion, our results show that napsin A is involved in the N-and C-terminal processing of proSP-B in type-II pneumocytes.The integrity and function of pulmonary surfactant are of paramount importance for lung function. Disturbance of surfactant activity leads to respiratory distress (1). The main function of pulmonary surfactant is the reduction of the surface tension at the air/liquid interface in the lung, thus preventing alveolar collapse at end-expiration. Pulmonary surfactant is a complex mixture of ϳ90% lipids and ϳ10% proteins that is synthesized, stored, secreted, and to a large extent recycled by type-II pneumocytes of the alveolar epithelium.The hydrophobic surfactant protein B (SP-B) 1 interacts with phospholipids and contributes to the formation of intracellular lamellar bodies, the structural rearrangement of secreted surfactant lipids into tubular myelin, as well as the subsequent rapid insertion of secreted surfactant phospholipids into the surface film (reviewed in Ref. 2). Hereditary SP-B deficiency in infants or mice leads to respiratory failure at birth (3-6). However, hereditary alveolar proteinosis in babies without any detectable mutations in the SP-B gene as well as acquired pulmonary alveolar proteinosis in children and adults are characterized by an intraalveolar accumulation of mature surfactant proteins and abnormal SP-B precursors. Furthermore, only SP-B precursors are detected in babies with congenital surfactant defects characterized by the absence of lamellar bodies in type-II pneumocytes.2 Therefore, insufficient processing of proSP-B due to a lack or dysfunction of one or more proteases involved in SP-B processing might be yet another undiscovered cause of surfactant dysfunction in p...

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Section: Fig 1 Localization Of Napsin a In The Human Lung By Immunomentioning

confidence: 99%

“…2). Hereditary SP-B deficiency in infants or mice leads to respiratory failure at birth (3)(4)(5)(6).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Involvement of Napsin A in the C- and N-terminal Processing of Surfactant Protein B in Type-II Pneumocytes of the Human Lung

Brasch

Ochs

Kähne

et al. 2003

Journal of Biological Chemistry

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“…Surfactant-associated water soluble proteins A and D (SP-A and SP-D, respectively) are important for host defense (3,4) but have less impact than the hydrophobic surfactant proteins on the biophysical properties of bilayers and monolayers. By contrast, the presence of hydrophobic surfactant proteins B and C (SP-B 1 and SP-C, respectively) is critical for optimizing surface tension reduction (5).…”

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confidence: 99%

NMR Structures of the C-Terminal Segment of Surfactant Protein B in Detergent Micelles and Hexafluoro-2-propanol

et al. 2004

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Although the membrane-associated surfactant protein B (SP-B) is an essential component of lung surfactant, which is itself essential for life, the molecular basis for its activity is not understood. SP-B's biophysical functions can be partially mimicked by subfragments of the protein, including the C-terminus. We have used NMR to determine the structure of a C-terminal fragment of human SP-B that includes residues 63-78. Structure determination was performed both in the fluorinated alcohol hexafluoro-2-propanol (HFIP) and in sodium dodecyl sulfate (SDS) micelles. In both solvents, residues 68-78 take on an amphipathic helical structure, in agreement with predictions made by comparison to homologous saposin family proteins. In HFIP, the five N-terminal residues of the peptide are largely unstructured, while in SDS micelles, these residues take on a well-defined compact conformation. Differences in helical residue side chain positioning between the two solvents were also found, with better agreement between the structures for the hydrophobic face than the hydrophilic face. A paramagnetic probe was used to investigate the position of the peptide within the SDS micelles and indicated that the peptide is located at the water interface with the hydrophobic face of the helix oriented inward, the hydrophilic face of the helix oriented outward, and the N-terminal residues even farther from the micelle center than those on the hydrophilic face of the R-helix. Interactions of basic residues of SP-B with anionic lipid headgroups are known to have an impact on function, and these studies demonstrate structural ramifications of such interactions via the differences observed between the peptide structures determined in HFIP and SDS.

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“…SP-A has been shown to be critical in synthesis and secretion of surfactant [34]. SP-B has a critical role in intracellular assembly of surfactant and spreading of surfactant onto the surface of the alveolar epithelium [35]. Antibody specific to each surfactant protein bound to bands corresponding to their respective molecular masses.…”

Section: Surfactant Protein Expressionmentioning

confidence: 99%

<i>Stachybotrys chartarum</i> (<i>atra</i>) spore extract alters surfactant protein expression and surfactant function in isolated fetal rat lung epithelial cells, fibroblasts and human A549 cells

Pollard¹,

Shaw²,

Sowa³

et al. 2013

OJPed

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Moulds, notably Stachybotrys chartarum (atra), are constant contributors to air pollution particularly to air quality in buildings. The spores themselves or their volatile organic products are present in variable amounts in almost all environments, particularly in buildings affected by flooding. These moulds and products can account for the sick building syndrome and have been tied to such occurrences as the outbreak of pulmonary hemosiderosis and hemorrhage in infants in Cleveland, Ohio. The present study was designed to investigate the effects of S. chartarum extracts on surfactant protein expression, surfactant quality and cell survival in the developing lung. S. chartarum extracts were incubated with cultures of several cell types; isolated fetal lung type II cells and fetal lung fibroblasts, and human lung A549 cells, a continuously growing cell line derived from surfactant producing type II alveolar cells. MTT formazan assays were employed to test cell viability. The synthesis and release of the predominant surfactant protein A (SP-A), which is involved in the regulation of surfactant turnover and metabolism, and surfactant protein B (SP-B) involved in shuttling phospholipids between surfactant subcompartments was also assessed. Antibodies to these proteins and western blotting results were used to assess the quantity of protein produced by the various cell types. A novel approach utilizing captive bubble surfactometry was employed to investigate the quality of surfactant in terms of surface tension and bubble volume measurements. Electron microscopy was used to examine changes in cellular structure of control and S. chartarum-treated cells. Results of the study showed that exposure to the S. chartarum extracts had deleterious effects on fetal lung epithelial cell viability and their ability to produce pulmonary surfactant. S. chartarum extracts also induced deleterious changes to the developing fetal lung cells in terms of expression of SP-A and SP-B as well as to the surface tension reducing abilities of the pulmonary surfactant. Ultrastructurally, spore toxin associated changes were apparent in the isolated lung cells most notably in the lamellar bodies of fetal rat lung alveolar type II and human A549 cells. This study has demonstrated the potential damage to surfactant production and function which may be induced by inhaling S. chartarum toxins.

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Structure and properties of surfactant protein B

Cited by 207 publications

References 44 publications

Involvement of Napsin A in the C- and N-terminal Processing of Surfactant Protein B in Type-II Pneumocytes of the Human Lung

Involvement of Napsin A in the C- and N-terminal Processing of Surfactant Protein B in Type-II Pneumocytes of the Human Lung

NMR Structures of the C-Terminal Segment of Surfactant Protein B in Detergent Micelles and Hexafluoro-2-propanol

<i>Stachybotrys chartarum</i> (<i>atra</i>) spore extract alters surfactant protein expression and surfactant function in isolated fetal rat lung epithelial cells, fibroblasts and human A549 cells

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Structure and properties of surfactant protein B

Cited by 207 publications

References 44 publications

Involvement of Napsin A in the C- and N-terminal Processing of Surfactant Protein B in Type-II Pneumocytes of the Human Lung

Involvement of Napsin A in the C- and N-terminal Processing of Surfactant Protein B in Type-II Pneumocytes of the Human Lung

NMR Structures of the C-Terminal Segment of Surfactant Protein B in Detergent Micelles and Hexafluoro-2-propanol

&lt;i&gt;Stachybotrys chartarum&lt;/i&gt; (&lt;i&gt;atra&lt;/i&gt;) spore extract alters surfactant protein expression and surfactant function in isolated fetal rat lung epithelial cells, fibroblasts and human A549 cells

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<i>Stachybotrys chartarum</i> (<i>atra</i>) spore extract alters surfactant protein expression and surfactant function in isolated fetal rat lung epithelial cells, fibroblasts and human A549 cells