Review: Structural determinants of pattern recognition by lung collectins

2010 ◽  
Vol 16 (3) ◽  
pp. 143-150 ◽  
Author(s):  
Barbara A. Seaton ◽  
Erika C. Crouch ◽  
Francis X. McCormack ◽  
James F. Head ◽  
Kevan L. Hartshorn ◽  
...  
Keyword(s):  
Lipid A ◽  
Protein A ◽  
Structural Similarity ◽  
Acute Phase Reactant ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Surfactant Protein D ◽  
Structural Determinants ◽  
Calcium Dependent ◽  
Anionic Phospholipids

Host defense roles for the lung collectins, surfactant protein A (SP-A) and surfactant protein D (SP-D), were first suspected in the 1980s when molecular characterization revealed their sequence homology to the acute phase reactant of serum, mannose-binding lectin. Surfactant protein A and SP-D have since been shown to play diverse and important roles in innate immunity and pulmonary homeostasis. Their location in surfactant ideally positions them to interact with air-space pathogens. Despite extensive structural similarity, the two proteins show many functional differences and considerable divergence in their interactions with microbial surface components, surfactant lipids, and other ligands. Recent crystallographic studies have provided many new insights relating to these observed differences. Although both proteins can participate in calcium-dependent interactions with sugars and other polyols, they display significant differences in the spatial orientation, charge, and hydrophobicity of their binding surfaces. Surfactant protein D appears particularly adapted to interactions with complex carbohydrates and anionic phospholipids, such as phosphatidylinositol. By contrast, SP-A shows features consistent with its preference for lipid ligands, including lipid A and the major surfactant lipid, dipalmitoylphosphatidylcholine. Current research suggests that structural biology approaches will help to elucidate the molecular basis of pulmonary collectin—ligand recognition and facilitate development of new therapeutics based upon SP-A and SP-D.

Assignment of the Human Pulmonary Surfactant Protein D Gene (SFTP4) to 10q22-q23 Close to the Surfactant Protein A Gene Cluster

Genomics ◽  
1993 ◽  
Vol 17 (2) ◽  
pp. 294-298 ◽  
Author(s):  
Konrad Kölble ◽  
Jinhua Lu ◽  
Sara E. Mole ◽  
Stefan Kaluz ◽  
Kenneth B.M. Reid
Keyword(s):  
Gene Cluster ◽  
Pulmonary Surfactant ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Surfactant Protein D ◽  
Pulmonary Surfactant Protein

scholarly journals Rat surfactant protein D enhances the production of oxygen radicals by rat alveolar macrophages

1992 ◽  
Vol 286 (1) ◽  
pp. 5-8 ◽  
Author(s):  
J F Van Iwaarden ◽  
H Shimizu ◽  
P H M Van Golde ◽  
D R Voelker ◽  
L M G Van Golde
Keyword(s):  
Alveolar Macrophages ◽  
Oxygen Radicals ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Surfactant Protein D ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Oxygen Radical Production ◽  
Stimulation Of

Rat surfactant protein D (SP-D) was shown to enhance the production of oxygen radicals by rat alveolar macrophages. This enhancement, which was determined by a lucigenin-dependent chemiluminescence assay, was maximal after 18 min at an SP-D concentration of 0.2 micrograms/ml. Surfactant lipids did not influence the stimulation of alveolar macrophages by SP-D, whereas the oxygen-radical production of these cells induced by surfactant protein A was inhibited by the lipids in a concentration-dependent manner.

scholarly journals Protective effect of extracorporeal membrane pulmonary oxygenation combined with cardiopulmonary resuscitation on post-resuscitation lung injury: a randomised controlled trial

2020 ◽  
Author(s):  
Jiyang Ling ◽  
Chunsheng Li ◽  
Yun Zhang ◽  
Xiaoli Yuan ◽  
Bo Liu ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Protein A ◽  
Surfactant Protein ◽  
Spontaneous Circulation ◽  
Clara Cell ◽  
Surfactant Protein A ◽  
Cell Protein ◽  
Surfactant Protein D ◽  
Lung Water ◽  
Pulmonary Vascular Permeability

Abstract Background: This work examines the protective effect and mechanisms of early extracorporeal membrane oxygenation with cardiopulmonary resuscitation (CPR) on ventricular-fibrillation-induced post-resuscitation lung injury in a swine cardiac-arrest model. Methods: Sixteen male swine were randomised to conventional CPR (CCPR; n=8; CCPR alone) and extracorporeal CPR (ECPR; n=8; extracorporeal membrane oxygenation with CCPR), with restoration of spontaneous circulation for 6 h as an endpoint. Serological specimens were collected at baseline and restoration of spontaneous circulation for 1, 2, 4, and 6 h; lung tissue specimens were obtained postmortem. Between-group comparisons of recovery success rate, extravascular lung water , pulmonary vascular permeability index, electron microscopic features, and serum and tissue biomarkers (surfactant protein A, surfactant protein D, Clara cell protein 16, superoxide dismutase, malondialdehyde, myeloperoxidase) were undertaken. Results: The CCPR group had non-significantly lower 6-h survival rate ( p> 0.05). Serum levels of surfactant protein A, surfactant protein D, Clara cell protein 16, and malondialdehyde were significantly higher ( p< 0.05), whereas serum superoxide dismutase was significantly lower, in the CCPR than in the ECPR group ( p <0.01). Compared with the ECPR group, tissue surfactant protein A, surfactant protein D, and superoxide dismutase significantly decreased compared to the baseline, whereas malondialdehyde and myeloperoxidase significantly increased ( p< 0.01) in the CCPR group. Extravascular lung water and pulmonary vascular permeability index were significantly higher in the CCPR after 6 h compared to the baseline values and the ECPR group ( p< 0.01). Conclusions: Electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and fuzzy lamellar structure and widening and blurring of the blood–gas barrier in the CCPR group in contrast to that in the ECPR group. ECPR was found to have protective pulmonary effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response post-resuscitation.

scholarly journals Role of P63 (CKAP4) in binding of surfactant protein-A to type II pneumocytes

2008 ◽  
Vol 295 (4) ◽  
pp. L658-L669 ◽  
Author(s):  
Sandra R. Bates ◽  
Altaf S. Kazi ◽  
Jian-Qin Tao ◽  
Kevin J. Yu ◽  
Daniel S. Gonder ◽  
...  
Keyword(s):  
Specific Binding ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Type Ii Cells ◽  
Type Ii ◽  
Calcium Dependent ◽  
Type Ii Pneumocytes ◽  
Surfactant Secretion

We have recently described a putative receptor for lung surfactant protein-A (SP-A) on rat type II pneumocytes. The receptor, P63, is a 63-kDa type II transmembrane protein. Coincubation of type II cells with P63 antibody (Ab) reversed the inhibitory effect of SP-A on secretagogue-stimulated surfactant secretion from type II cells. To further characterize SP-A interactions with P63, we expressed recombinant P63 protein in Escherichia coli and generated antibodies to P63. Immunogold electron microscopy confirmed endoplasmic reticulum and plasma membrane localization of P63 in type II cells with prominent labeling of microvilli. Binding characteristics of iodinated SP-A to type II cells in the presence of P63 Ab were determined. Binding (4°C, 1 h) of 125I-SP-A to type II cells demonstrated both specific (calcium-dependent) and nonspecific (calcium-independent) components. Ab to P63 protein blocked the specific binding of 125I-SP-A to type II cells and did not change the nonspecific SP-A association. A549 cells, a pneumocyte model cell line, expressed substantial levels of P63 and demonstrated specific binding of 125I-SP-A that was inhibited by the P63 Ab. The secretagogue (cAMP)-stimulated increase in calcium-dependent binding of SP-A to type II cells was blocked by the presence of P63 Ab. Transfection of type II cells with small interfering RNA to P63 reduced P63 protein expression, attenuated P63-specific SP-A binding, and reversed the ability of SP-A to prevent surfactant secretion from the cells. Our results further substantiate the role of P63 as an SP-A receptor protein localized on the surface of lung type II cells.

Efficient resolution of Pneumocystis murina infection in surfactant protein A-deficient mice following withdrawal of corticosteroid-induced immunosuppression

2006 ◽  
Vol 55 (2) ◽  
pp. 143-147 ◽  
Author(s):  
Michael Linke ◽  
Alan Ashbaugh ◽  
Judith Koch ◽  
Reiko Tanaka ◽  
Peter Walzer
Keyword(s):  
Protein A ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Lung Lavage ◽  
Surfactant Protein A ◽  
Surfactant Protein D ◽  
Wild Type ◽  
Enhanced Expression ◽  
Lymphocyte Populations ◽  
Deficient Mice

Following withdrawal of immunosuppression, surfactant protein A (SP-A)-deficient and wild-type mice cleared Pneumocystis murina infection in a similar manner, but exhibited significant differences in lymphocyte populations, interleukin (IL)-6 levels and chemokine expression levels. A higher percentage of lymphocytes were detected in lung lavage fluid from SP-A-deficient mice, but more CD4+ T cells were isolated from lung tissue of wild-type mice. Higher concentrations of IL-6 were detected in lavage fluid and enhanced expression of lymphotactin and RANTES were detected in the lungs of wild-type mice. Equal levels of surfactant protein D were detected in SP-A-deficient and wild-type mice and no differences were detected in markers of lung injury between the two strains of mice. Thus, SP-A does not enhance organism clearance, but does modulate the host immune response during resolution of P. murina infection.

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