Content-dependent activity of lung surfactant protein B  in mixtures with lipids

The content-dependent activity of surfactant protein (SP)-B was studied in mixtures with dipalmitoyl phosphatidylcholine (DPPC), synthetic lipids (SL), and purified phospholipids (PPL) from calf lung surfactant extract (CLSE). At fixed SP-B content, adsorption and dynamic surface tension lowering were ordered as PPL/SP-B ≈ SL/SP-B > DPPC/SP-B. All mixtures were similar in having increased surface activity as SP-B content was incrementally raised from 0.05 to 0.75% by weight. SP-B had small but measurable effects on interfacial properties even at very low levels ≤0.1% by weight. PPL/SP-B (0.75%) had the highest adsorption and dynamic surface activity, approaching the behavior of CLSE. All mixtures containing 0.75% SP-B reached minimum surface tensions <1 mN/m in pulsating bubble studies at low phospholipid concentration (1 mg/ml). Mixtures of PPL or SL with SP-B (0.5%) also had minimum surface tensions <1 mN/m at 1 mg/ml, whereas DPPC/SP-B (0.5%) reached <1 mN/m at 2.5 mg/ml. Physiological activity also was strongly dependent on SP-B content. The ability of instilled SL/SP-B mixtures to improve surfactant-deficient pressure-volume mechanics in excised lavaged rat lungs increased as SP-B content was raised from 0.1 to 0.75% by weight. This study emphasizes the crucial functional activity of SP-B in lung surfactants. Significant differences in SP-B content between exogenous surfactants used to treat respiratory disease could be associated with substantial activity variations.

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Surface activity of a synthetic lung surfactant containing a phospholipase-resistant phosphonolipid analog of dipalmitoyl phosphatidylcholine

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00346.2002 ◽

2003 ◽

Vol 285 (3) ◽

pp. L550-L559 ◽

Cited By ~ 16

Author(s):

Z. Wang ◽

A. L. Schwan ◽

L. L. Lairson ◽

J. S. O'Donnell ◽

G. F. Byrne ◽

...

Keyword(s):

Serum Albumin ◽

Surface Activity ◽

Dynamic Compression ◽

Lung Surfactant ◽

Dynamic Surface Tension ◽

Surfactant Proteins ◽

Chemical Degradation ◽

Dynamic Surface ◽

Dipalmitoyl Phosphatidylcholine ◽

Surfactant Dysfunction

Surface activity and sensitivity to inhibition from phospholipase A2 (PLA2), lysophosphatidylcholine (LPC), and serum albumin were studied for a synthetic C16:0 diether phosphonolipid (DEPN-8) combined with 1.5% by weight of mixed hydrophobic surfactant proteins (SP)-B/C purified from calf lung surfactant extract (CLSE). Pure DEPN-8 had better adsorption and film respreading than the major lung surfactant phospholipid dipalmitoyl phosphatidylcholine and reached minimum surface tensions <1 mN/m under dynamic compression on the Wilhelmy balance and on a pulsating bubble surfactometer (37°C, 20 cycles/min, 50% area compression). DEPN-8 + 1.5% SP-B/C exhibited even greater adsorption and had overall dynamic surface tension lowering equal to CLSE on the bubble. In addition, films of DEPN-8 + 1.5% SP-B/C on the Wilhelmy balance had better respreading than CLSE after seven (but not two) cycles of compression-expansion at 23°C. DEPN-8 is structurally resistant to degradation by PLA2, and DEPN-8 + 1.5% SP-B/C maintained high adsorption and dynamic surface activity in the presence of this enzyme. Incubation of CLSE with PLA2 led to chemical degradation, generation of LPC, and reduced surface activity. DEPN-8 + 1.5% SP-B/C was also more resistant than CLSE to direct biophysical inhibition by LPC, and the two were similar in their sensitivity to biophysical inhibition by serum albumin. These findings indicate that synthetic surfactants containing DEPN-8 combined with surfactant proteins or related synthetic peptides have potential utility for treating surfactant dysfunction in inflammatory lung injury.

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Lipid composition greatly affects the in vitro surface activity of lung surfactant protein mimics

Colloids and Surfaces B Biointerfaces ◽

10.1016/j.colsurfb.2007.01.001 ◽

2007 ◽

Vol 57 (1) ◽

pp. 37-55 ◽

Cited By ~ 16

Author(s):

Shannon L. Seurynck-Servoss ◽

Nathan J. Brown ◽

Michelle T. Dohm ◽

Cindy W. Wu ◽

Annelise E. Barron

Keyword(s):

Surface Activity ◽

Lipid Composition ◽

Lung Surfactant ◽

Surfactant Protein ◽

Protein Mimics ◽

Lung Surfactant Protein

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Inhibition of surfactant activity byPneumocystis cariniiorganisms and components in vitro

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00453.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. L1124-L1131 ◽

Cited By ~ 5

Author(s):

Zhengdong Wang ◽

Adam Foye ◽

Yusuo Chang ◽

Patricia R. Chess ◽

Terry W. Wright ◽

...

Keyword(s):

Surface Tension ◽

Surface Activity ◽

Total Phospholipid ◽

Lung Surfactant ◽

Pneumocystis Carinii ◽

Protein A ◽

Dynamic Surface Tension ◽

Chemical Components ◽

Dynamic Surface

This study examines the direct inhibitory effects of Pneumocystis carinii ( Pc) organisms and chemical components on the surface activity and composition of whole calf lung surfactant (WLS) and calf lung surfactant extract (CLSE) in vitro. Incubation of WLS suspensions with intact Pc organisms (107per milligram of surfactant phospholipid) did not significantly alter total phospholipid levels or surfactant protein A content. Incubation with intact Pc organisms also did not impair dynamic surface tension lowering in suspensions of WLS or centrifuged large surfactant aggregates on a bubble surfactometer (37°C, 20 cycles/min, 0.5 and 2.5 mg phospholipid/ml). However, exposure of WLS or CLSE to disrupted (sonicated) Pc organisms led to severe detriments in activity, with minimum surface tensions of 17–19 mN/m vs. <1 mN/m for surfactants alone. Extracted hydrophobic chemical components from Pc (98.8% lipids, 0.1 mM) reduced the surface activity of WLS and CLSE similarly to sonicated Pc organisms, whereas extracted hydrophilic chemical components from Pc (primarily proteins) had only minor effects on surface tension lowering. These results indicate that in addition to surfactant dysfunction induced by inflammatory lung injury and edema-derived inhibitors in Pc pneumonia, disrupted Pc organisms in the alveolar lumen also have the potential to directly inhibit endogenous and exogenous lung surfactants in affected patients.

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Activity and biophysical inhibition resistance of a novel synthetic lung surfactant containing Super-Mini-B DATK peptide

PeerJ ◽

10.7717/peerj.1528 ◽

2016 ◽

Vol 4 ◽

pp. e1528 ◽

Cited By ~ 4

Author(s):

Robert H. Notter ◽

Zhengdong Wang ◽

Frans J. Walther

Keyword(s):

Fatty Acids ◽

Surface Tension ◽

Free Fatty Acids ◽

Surface Activity ◽

Dynamic Compression ◽

Physiological Activity ◽

Lung Surfactant ◽

Synthetic Surfactant ◽

Dynamic Surface ◽

Surfactant Deficiency

Background/objectives.This study examines the surface activity, resistance to biophysical inhibition, and pulmonary efficacy of a synthetic lung surfactant containing glycerophospholipids combined with Super Mini-B (S-MB) DATK, a novel and stable molecular mimic of lung surfactant protein (SP)-B. The objective of the work is to test whether S-MB DATK synthetic surfactant has favorable biophysical and physiological activity for future use in treating surfactant deficiency or dysfunction in lung disease or injury.Methods.The structure of S-MB DATK peptide was analyzed by homology modeling and by FTIR spectroscopy. Thein vitrosurface activity and inhibition resistance of synthetic S-MB DATK surfactant was assessed in the presence and absence of albumin, lysophosphatidylcholine (lyso-PC), and free fatty acids (palmitoleic and oleic acid). Adsorption and dynamic surface tension lowering were measured with a stirred subphase dish apparatus and a pulsating bubble surfactometer (20 cycles/min, 50% area compression, 37 °C).In vivopulmonary activity of S-MB DATK surfactant was measured in ventilated rabbits with surfactant deficiency/dysfunction induced by repeated lung lavages that resulted in arterial PO2values <100 mmHg.Results.S-MB DATK surfactant had very high surface activity in all assessments. The preparation adsorbed rapidly to surface pressures of 46–48 mN/m at 37 °C (low equilibrium surface tensions of 22–24 mN/m), and reduced surface tension to <1 mN/m under dynamic compression on the pulsating bubble surfactometer. S-MB DATK surfactant showed a significant ability to resist inhibition by serum albumin, C16:0 lyso-PC, and free fatty acids, but surfactant inhibition was mitigated by increasing surfactant concentration. S-MB DATK synthetic surfactant quickly improved arterial oxygenation and lung compliance after intratracheal instillation to ventilated rabbits with severe surfactant deficiency.Conclusions.S-MB DATK is an active mimic of native SP-B. Synthetic surfactants containing S-MB DATK (or related peptides) combined with lipids appear to have significant future potential for treating clinical states of surfactant deficiency or dysfunction, such as neonatal and acute respiratory distress syndromes.

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