scholarly journals Surfactant protein B inhibits secretory phospholipase A2 hydrolysis of surfactant phospholipids

2012 ◽  
Vol 302 (2) ◽  
pp. L257-L265 ◽  
Author(s):  
R. Duncan Hite ◽  
Bonnie L. Grier ◽  
B. Moseley Waite ◽  
Ruud A. Veldhuizen ◽  
Fred Possmayer ◽  
...  
Keyword(s):  
Protein A ◽  
Lipid Vesicles ◽  
Surfactant Protein ◽  
Airway Diseases ◽  
Surfactant Protein B ◽  
Monomolecular Films ◽  
Alveolar Surfactant ◽  
Surfactant Phospholipids ◽  
Air Liquid Interface ◽  
Hydrolysis Of

Hydrolysis of surfactant phospholipids (PL) by secretory phospholipases A2 (sPLA2) contributes to surfactant damage in inflammatory airway diseases such as acute lung injury/acute respiratory distress syndrome. We and others have reported that each sPLA2 exhibits specificity in hydrolyzing different PLs in pulmonary surfactant and that the presence of hydrophilic surfactant protein A (SP-A) alters sPLA2-mediated hydrolysis. This report tests the hypothesis that hydrophobic SP-B also inhibits sPLA2-mediated surfactant hydrolysis. Three surfactant preparations were used containing varied amounts of SP-B and radiolabeled tracers of phosphatidylcholine (PC) or phosphatidylglycerol (PG): 1) washed ovine surfactant (OS) (pre- and postorganic extraction) compared with Survanta (protein poor), 2) Survanta supplemented with purified bovine SP-B (1–5%, wt/wt), and 3) a mixture of dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) (DPPC:POPC:POPG, 40:40:20) prepared as vesicles and monomolecular films in the presence or absence of SP-B. Hydrolysis of PG and PC by Group IB sPLA2 (PLA2G1A) was significantly lower in the extracted OS, which contains SP-B, compared with Survanta ( P = 0.005), which is SP-B poor. Hydrolysis of PG and PC in nonextracted OS, which contains all SPs, was lower than both Survanta and extracted OS. When Survanta was supplemented with 1% SP-B, PG and PC hydrolysis by PLA2G1B was significantly lower ( P < 0.001) than in Survanta alone. When supplemented into pure lipid vesicles and monomolecular films composed of PG and PC mixtures, SP-B also inhibited hydrolysis by both PLA2G1B and Group IIA sPLA2 (PLA2G2A). In films, PLA2G1B hydrolyzed surfactant PL monolayers at surface pressures ≤30 mN/m ( P < 0.01), and SP-B lowered the surface pressure range at which hydrolysis can occur. These results suggest the hydrophobic SP, SP-B, protects alveolar surfactant PL from hydrolysis mediated by multiple sPLA2 in both vesicles (alveolar subphase) and monomolecular films (air-liquid interface).

Antisense inhibition of surfactant protein A decreases tubular myelin formation in human fetal lung in vitro

2002 ◽  
Vol 282 (3) ◽  
pp. L386-L393 ◽  
Author(s):  
Jonathan M. Klein ◽  
Troy A. McCarthy ◽  
John M. Dagle ◽  
Jeanne M. Snyder
Keyword(s):  
Gene Expression ◽  
Protein A ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Mrna Levels ◽  
Phosphorothioate Oligonucleotide ◽  
Myelin Formation ◽  
Surfactant Phospholipids ◽  
Human Fetal Lung

Surfactant protein A (SP-A) is the most abundant of the surfactant-associated proteins. SP-A is involved in the formation of tubular myelin, the modulation of the surface tension-reducing properties of surfactant phospholipids, the metabolism of surfactant phospholipids, and local pulmonary host defense. We hypothesized that elimination of SP-A would alter the regulation of SP-B gene expression and the formation of tubular myelin. Midtrimester human fetal lung explants were cultured for 3–5 days in the presence or absence of an antisense 18-mer phosphorothioate oligonucleotide (ON) complementary to SP-A mRNA. After 3 days in culture, SP-A mRNA was undetectable in antisense ON-treated explants. After 5 days in culture, levels of SP-A protein were also decreased by antisense treatment. SP-B mRNA levels were not affected by the antisense SP-A ON treatment. However, there was decreased tubular myelin formation in the antisense SP-A ON-treated tissue. We conclude that selective elimination of SP-A mRNA and protein results in a decrease in tubular myelin formation in human fetal lung without affecting SP-B mRNA. We speculate that SP-A is critical to the formation of tubular myelin during human lung development and that the regulation of SP-B gene expression is independent of SP-A gene expression.

Human surfactant protein B: structure, function, regulation, and genetic disease

1995 ◽  
Vol 75 (4) ◽  
pp. 749-757 ◽  
Author(s):  
J. A. Whitsett ◽  
L. M. Nogee ◽  
T. E. Weaver ◽  
A. D. Horowitz
Keyword(s):  
Gene Expression ◽  
Surfactant Protein ◽  
Structure And Function ◽  
Respiratory Epithelial Cell ◽  
Surfactant Protein B ◽  
Cell Gene Expression ◽  
Surfactant Phospholipids ◽  
And Function ◽  
Respiratory Epithelial ◽  
Cell Gene

Elucidation of the structure and function of the hydrophobic surfactant protein (SP-B) and the SP-B gene has provided critical insight into surfactant homeostasis and control of respiratory epithelial cell gene expression. Surfactant protein B, in concert with surfactant protein A (SP-A), surfactant protein C (SP-C), and surfactant phospholipids, contributes to the structure and function of surfactant particles, determining surface activities and pathways by which surfactant phospholipids and proteins are processed, routed, packaged, and secreted from lamellar bodies by type II epithelial cells. After secretion, SP-B plays an essential role in determining the structure of tubular myelin, the stability and rapidity of spreading, and the recycling of surfactant phospholipids. The biochemical and structural signals underlying the homeostasis of alveolar surfactant are likely mediated by interactions between the surfactant proteins and phospholipids producing discrete structural forms that vary in size, aproprotein, and phospholipid content. Distinctions in structure, protein, and size are likely to determine the function of surfactant particles, their catabolism, or recycling by alveolar macrophages and airway epithelial cells. Analysis of the genetic controls governing the SP-B gene has led to the definition of DNA-protein interactions that determine respiratory epithelial cell gene expression in general. The important role of SP-B in lung function was defined by the study of a lethal neonatal respiratory disease, hereditary SP-B deficiency, caused by mutations in the human SP-B gene.

scholarly journals Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating cytotoxin fromMycoplasma pneumoniae

2015 ◽  
Vol 112 (16) ◽  
pp. 5165-5170 ◽  
Author(s):  
Argentina Becker ◽  
T. R. Kannan ◽  
Alexander B. Taylor ◽  
Olga N. Pakhomova ◽  
Yanfeng Zhang ◽  
...  
Keyword(s):  
Membrane Lipids ◽  
Protein A ◽  
Surfactant Protein ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Surface Binding ◽  
Vacuolating Cytotoxin ◽  
Airway Diseases ◽  
Adp Ribosyltransferase ◽  
Cards Toxin

Mycoplasma pneumoniae(Mp) infections cause tracheobronchitis and “walking” pneumonia, and are linked to asthma and other reactive airway diseases. As part of the infectious process, the bacterium expresses a 591-aa virulence factor with both mono-ADP ribosyltransferase (mART) and vacuolating activities known as Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TX binds to human surfactant protein A and annexin A2 on airway epithelial cells and is internalized, leading to a range of pathogenetic events. Here we present the structure of CARDS TX, a triangular molecule in which N-terminal mART and C-terminal tandem β-trefoil domains associate to form an overall architecture distinct from other well-recognized ADP-ribosylating bacterial toxins. We demonstrate that CARDS TX binds phosphatidylcholine and sphingomyelin specifically over other membrane lipids, and that cell surface binding and internalization activities are housed within the C-terminal β-trefoil domain. The results enhance our understanding ofMppathogenicity and suggest a novel avenue for the development of therapies to treatMp-associated asthma and other acute and chronic airway diseases.

Type II pneumocytes secrete vitamin E together with surfactant lipids

1993 ◽  
Vol 265 (2) ◽  
pp. L133-L139 ◽  
Author(s):  
B. Rustow ◽  
R. Haupt ◽  
P. A. Stevens ◽  
D. Kunze
Keyword(s):  
Vitamin E ◽  
Palmitic Acid ◽  
Lung Surfactant ◽  
Protein A ◽  
Specific Radioactivity ◽  
Surfactant Protein ◽  
Lung Lavage ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Surfactant

Lung surfactant is exposed to strongly oxidizing conditions. We examined the hypothesis that in lung, lipophilic antioxidants are secreted together with surfactant to counteract the peroxidation of surfactant constituents. Lung lavage and the subfractions of the alveolar surfactant contain the lipophilic antioxidants vitamin E, vitamin A, and plasmalogens. The specific radioactivity of vitamin E isolated from serum, lung homogenate, lamellar bodies, and lung lavage increased linearly up to 3 h after intraperitoneal application of [3H]tocopherol. [3H]tocopherol was secreted in situ together with [14C]palmitic acid-labeled phospholipid in response to isoproterenol. Type II cells cultured in presence of [3H]tocopherol or of [3H]cholecalciferol and [14C]palmitic acid responded to isoproterenol by a time-dependent increase in secretion of [3H]tocopherol and of 14C-labeled phospholipids but not of [3H]cholecalciferol. The isoproterenol-stimulated secretion of [3H]tocopherol and of 14C-labeled phospholipids by type II cells is inhibited by surfactant protein A. We conclude that the alveolar surfactant contains lipophilic antioxidants as integral constituents. [3H]tocopherol seems to be secreted together with surfactant.

SP-B refining of pulmonary surfactant phospholipid films

1999 ◽  
Vol 277 (6) ◽  
pp. L1179-L1189 ◽  
Author(s):  
Kaushik Nag ◽  
James G. Munro ◽  
Kevin Inchley ◽  
Samuel Schürch ◽  
Nils O. Petersen ◽  
...  
Keyword(s):  
Pulmonary Surfactant ◽  
Film Formation ◽  
Surfactant Protein ◽  
Neutral System ◽  
Area Reduction ◽  
Surfactant Protein B ◽  
Squeeze Out ◽  
Planar Films ◽  
Surfactant Phospholipids ◽  
Film Area

Pulmonary surfactant stabilizes the alveoli by lining the air-fluid interface with films that reduce surface tension to near 0 mN/m (γmin). Surfactant protein B (SP-B) enhances the surface activity of surfactant phospholipids. A captive bubble tensiometer (CBT) was used to study the properties of adsorbed films of dipalmitoylphosphatidylcholine (DPPC) with acidic 1-palmitoyl-2-oleoyl- sn-glycero-3-[phospho- rac-(1-glycerol)] (POPG) or neutral 1-palmitoyl-2-oleoyl- sn-glycerol-3-phosphocholine with (7:3) and without 1% dimeric SP-B. SP-B enhanced the adsorption rate of DPPC-containing neutral or acidic lipid suspensions (1 mg/ml) to a similar extent. Quasi-static cycling of these films revealed that SP-B significantly decreased the film area reduction required to reach γmin for the acidic but not for the neutral system. The results obtained with DPPC-phosphatidylglycerol (PG)-SP-B were consistent with selective DPPC adsorption into the surface monolayer during film formation. Film area reduction required to reach γmin with this system (with and without calcium) approached that of pure DPPC, suggesting selective DPPC insertion and PG squeeze-out. Dynamic cycling of such films showed that larger film area reductions were required to reach γmin for the neutral than for acidic system, even after 20 cycles. Fluorescence microscopy of solvent-spread DPPC-POPG-SP-B planar films revealed highly condensed structures at ∼25 mN/m, although no specific PG phase-segregated structures could be identified. The study suggests that specific interactions of SP-B with acidic phospholipids of surfactant may be involved in the generation and maintenance of DPPC-rich films in the alveoli.

Dipalmitoylphosphatidylcholine is not the major surfactant phospholipid species in all mammals

2005 ◽  
Vol 289 (5) ◽  
pp. R1426-R1439 ◽  
Author(s):  
Carol J. Lang ◽  
Anthony D. Postle ◽  
Sandra Orgeig ◽  
Fred Possmayer ◽  
Wolfgang Bernhard ◽  
...  
Keyword(s):  
Thermal Behavior ◽  
Animal Species ◽  
Protein A ◽  
Complex Mixture ◽  
Surfactant Protein ◽  
Tasmanian Devil ◽  
Surfactant Protein B ◽  
Surfactant Composition ◽  
Phospholipid Species

Pulmonary surfactant, a complex mixture of lipids and proteins, lowers the surface tension in terminal air spaces and is crucial for lung function. Within an animal species, surfactant composition can be influenced by development, disease, respiratory rate, and/or body temperature. Here, we analyzed the composition of surfactant in three heterothermic mammals (dunnart, bat, squirrel), displaying different torpor patterns, to determine: 1) whether increases in surfactant cholesterol (Chol) and phospholipid (PL) saturation occur during long-term torpor in squirrels, as in bats and dunnarts; 2) whether surfactant proteins change during torpor; and 3) whether PL molecular species (molsp) composition is altered. In addition, we analyzed the molsp composition of a further nine mammals (including placental/marsupial and hetero-/homeothermic contrasts) to determine whether phylogeny or thermal behavior determines molsp composition in mammals. We discovered that like bats and dunnarts, surfactant Chol increases during torpor in squirrels. However, changes in PL saturation during torpor may not be universal. Torpor was accompanied by a decrease in surfactant protein A in dunnarts and squirrels, but not in bats, whereas surfactant protein B did not change in any species. Phosphatidylcholine (PC)16:0/16:0 is highly variable between mammals and is not the major PL in the wombat, dunnart, shrew, or Tasmanian devil. An inverse relationship exists between PC16:0/16:0 and two of the major fluidizing components, PC16:0/16:1 and PC16:0/14:0. The PL molsp profile of an animal species is not determined by phylogeny or thermal behavior. We conclude that there is no single PL molsp composition that functions optimally in all mammals; rather, surfactant from each animal is unique and tailored to the biology of that animal.

Filaments of surfactant protein A specifically interact with corrugated surfaces of phospholipid membranes

1999 ◽  
Vol 276 (4) ◽  
pp. L631-L641 ◽  
Author(s):  
Nades Palaniyar ◽  
Ross A. Ridsdale ◽  
Stephen A. Hearn ◽  
Yew Meng Heng ◽  
F. Peter Ottensmeyer ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Protein A ◽  
Lipid Vesicles ◽  
Surfactant Protein ◽  
Uranyl Acetate ◽  
Lipid Vesicle ◽  
Transmission Electron

Pulmonary surfactant, a mixture of lipids and surfactant proteins (SPs), plays an important role in respiration and gas exchange. SP-A, the major SP, exists as an octadecamer that can self-associate to form elongated protein filaments in vitro. We have studied here the association of purified bovine SP-A with lipid vesicle bilayers in vitro with negative staining with uranyl acetate and transmission electron microscopy. Native bovine surfactant was also examined by transmission electron microscopy of thinly sectioned embedded material. Lipid vesicles made from dipalmitoylphosphatidylcholine and egg phosphatidylcholine (1:1 wt/wt) generally showed a smooth surface morphology, but some large vesicles showed a corrugated one. On the smooth-surfaced vesicles, SP-As primarily interacted in the form of separate octadecamers or as multidirectional protein networks. On the surfaces of the striated vesicles, SP-As primarily formed regularly spaced unidirectional filaments. The mean spacing between adjacent striations and between adjacent filaments was 49 nm. The striated surfaces were not essential for the formation of filaments but appeared to stabilize them. In native surfactant preparations, SP-A was detected in the dense layers. This latter arrangement of the lipid bilayer-associated SP-As supported the potential relevance of the in vitro structures to the in vivo situation.

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