Interaction of transferrin saturated with iron with lung surfactant in respiratory failure

1994 ◽  
Vol 77 (2) ◽  
pp. 757-766 ◽  
Author(s):  
M. Hallman ◽  
A. Sarnesto ◽  
K. Bry
Keyword(s):  
Respiratory Failure ◽  
Surface Activity ◽  
Lung Surfactant ◽  
Protein A ◽  
Surfactant Protein ◽  
Lung Damage ◽  
Epithelial Lining ◽  
Surface Absorption ◽  
Epithelial Lining Fluid

Proteins that decrease the surface activity of surfactant accumulate in epithelial lining fluid in respiratory failure. The aim of this study was to isolate a surfactant inhibitor from the airways of rabbits in acute respiratory failure induced by bronchoalveolar lavage (BAL). This inhibitor was identified as being transferrin (TF). Unlike serum TF, TF recovered in respiratory failure was saturated with iron (Fe(3+)-TF). Fe(3+)-TF decreased the surface activity of normal surfactant in vitro, whereas iron-free TF had no effect. In the presence of H2O2 and a reducing agent, Fe(+3)-TF inactivated the surfactant complex: the surface absorption rate was decreased, immunoreactive surfactant protein A was decreased, and malondialdehyde was formed. The acute effects of Fe(3+)-TF and iron-free TF applied to the airways were studied in animal models. In respiratory failure induced by BAL, Fe(3+)-TF deteriorated respiratory failure, whereas iron-free TF had no effect. In respiratory failure induced by hyperoxia for 48 h, administration of iron-free TF ameliorated the respiratory failure and improved the surface activity in BAL. We propose that Fe(3+)-TF accumulating in epithelial lining fluid during lung damage contributes to surfactant inhibition and promotes the formation of free radicals that inactivate the surfactant system.

scholarly journals Surfactant dysfunction after inhalation of nitric oxide

1996 ◽  
Vol 80 (6) ◽  
pp. 2026-2034 ◽  
Author(s):  
M. Hallman ◽  
F. Waffarn ◽  
K. Bry ◽  
R. Turbow ◽  
M. T. Kleinman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Surface Activity ◽  
Protein S ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid ◽  
Iron Saturation ◽  
Minimum Surface Tension ◽  
Surfactant Dysfunction ◽  
Inhaled No

To study whether nitric oxide (NO) affects surfactant function, 36 young rats inhaled one of the following humidified environments for 24 h: 1) air; 2) 95% O2; 3) air and 100 parts/million (ppm) NO; and 4) 95% O2 and 100 ppm NO. The treatments did not change the recovery of phospholipid from bronchoalveolar lavage (BAL). Exposure to NO of animals that breathed either air or 95% O2 increased the minimum surface tension of surfactant from BAL at low (1.5 mumol/ml), but not at high (4 mumol/ml), phosphatidylcholine concentration. After inhaled NO, the nonsedimentable protein of BAL decreased the surface activity of surfactant (1 mumol phosphatidylcholine/ml) more than the protein from the controls. NO treatment of animals that breathed either air or 95% O2 affected neither the quantity nor the molecular weight distribution of nonsedimentable protein. Hyperoxia increased the amount of the nonsedimentable protein, whereas NO increased the iron saturation of transferrin. The surfactant fraction and the nonsedimentable protein from BAL were separately exposed to 80 ppm NO in vitro. NO exposure had no effect on the surface activity of surfactant fraction. NO exposure of nonsedimentable protein from the control animals (no NO) increased the inhibition of the surface activity and changed the adsorption spectrum of the protein, suggesting conversion of hemoglobin to methemoglobin. Nonsedimentable protein from NO-exposed animals contained methemoglobin. We propose that surfactant dysfunction caused by inhaled NO is in part due to alteration of protein(s) in epithelial lining fluid that in turn inactivates surfactant.

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

2007 ◽  
Vol 57 (1) ◽  
pp. 37-55 ◽  
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

A Synthetic Segment of Surfactant Protein A: Structure, in Vitro Surface Activity, and in Vivo Efficacy

1996 ◽  
Vol 39 (6) ◽  
pp. 938-946 ◽  
Author(s):  
Frans J Walther ◽  
Remedios David-Cu ◽  
Carol Leung ◽  
Roberta Bruni ◽  
José Hernández-Juviel ◽  
...  
Keyword(s):  
Surface Activity ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
In Vivo Efficacy

Inhibition of surfactant activity byPneumocystis cariniiorganisms and components in vitro

2005 ◽  
Vol 288 (6) ◽  
pp. L1124-L1131 ◽  
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.

scholarly journals Pharmacodynamics of Moxifloxacin and Levofloxacin at Simulated Epithelial Lining Fluid Drug Concentrations against Streptococcus pneumoniae

2004 ◽  
Vol 48 (4) ◽  
pp. 1215-1221 ◽  
Author(s):  
Naomi R. Florea ◽  
Pamela R. Tessier ◽  
Cuilian Zhang ◽  
Charles H. Nightingale ◽  
David P. Nicolau
Keyword(s):  
Streptococcus Pneumoniae ◽  
Fluoroquinolone Resistance ◽  
Epithelial Lining ◽  
Time Curve ◽  
Bacterial Killing ◽  
Epithelial Lining Fluid ◽  
Log Reduction ◽  
Development Of Resistance ◽  
Drug Concentrations

ABSTRACT Recent clinical failures associated with levofloxacin treatment for Streptococcus pneumoniae infections and growing evidence of frequent mutations in the isolate population have led to increased concerns regarding fluoroquinolone resistance. Our objective was to characterize the efficacies of levofloxacin and moxifloxacin against various genotypes of S. pneumoniae after simulated bronchopulmonary exposures. An in vitro model was used to simulate a levofloxacin concentration of 500 mg and a moxifloxacin concentration of 400 mg, which were previously determined to be the concentrations in the epithelial lining fluid of older adults receiving once-daily dosing. The effects of the drugs were tested against six S. pneumoniae containing various mutations. Bacterial density and resistance were quantitatively assessed over 48 h. The S. pneumoniae isolate with no mutation displayed a 4-log reduction in CFU after treatment with both agents and did not develop resistance. Isolates containing the parC or parE mutation or both mutations regrew and developed resistance when they were exposed to levofloxacin, despite an unbound area under the concentration-time curve (AUC):MIC ratio of ∼100. When the isolate containing the parC and gyrA mutations was exposed to levofloxacin, there was a half-log reduction in the number of CFU compared to that for the control, but the isolate subsequently regrew. Likewise, levofloxacin did not kill the isolate containing the parC, gyrA, and parE mutations. Moxifloxacin sustained the killing of all bacterial isolates tested without the development of resistance. Levofloxacin did not sustain bacterial killing and did not prevent the emergence of further resistance in mutants with the parC or parE mutation or both mutations, even though an unbound AUC:MIC ratio for exposure well above the breakpoint of 30 to 40 established in the literature for S. pneumoniae was maintained. Moxifloxacin was effective against all isolates tested, despite the presence of isolates with two- and three-step mutations, for which the MICs were increased.

Regulation of lung surfactant secretion

1990 ◽  
Vol 258 (6) ◽  
pp. L241-L253 ◽  
Author(s):  
A. Chander ◽  
A. B. Fisher
Keyword(s):  
Lung Surfactant ◽  
Protein A ◽  
Lamellar Body ◽  
Surfactant Protein ◽  
Ventilation Rate ◽  
Future Research ◽  
Surfactant Secretion ◽  
Vasopressin Receptors ◽  
Protein Components

Secretion of lung surfactant is the direct step in release of the lipoprotein-like product, synthesized in lung epithelial type II cells, onto the alveolar surface. Release of surfactant phosphatidylcholine (PC) proceeds via formation of surface pores during exocytosis of lamellar bodies. Surfactant secretion is regulated locally in the lung by changes in ventilation rate, possibly mediated by distension and altered intracellular pH. Secretion is also stimulated by various agents, including agonists for beta-adrenergic, purinoceptors, and vasopressin receptors and is associated with increased cytosolic Ca2+, cellular adenosine 3',5'-cyclic monophosphate, and activation of protein kinases. Limited studies suggest that secretion of surfactant protein A may be regulated by both cAMP-dependent and protein kinase C-dependent pathways. The integration of these various mechanisms for the in vivo regulation of surfactant secretion remains largely unexplored. Future research into the mechanisms involved in lamellar body fusion with the plasma membrane, role of protein phosphorylation, transient changes in cAMP and Ca2+, and coordination between the secretion of phospholipid and protein components of surfactant should enhance our understanding of secretion of surfactant “lipoprotein.”

Surfactant metabolism in surfactant protein A-deficient mice

1997 ◽  
Vol 272 (3) ◽  
pp. L479-L485 ◽  
Author(s):  
M. Ikegami ◽  
T. R. Korfhagen ◽  
M. D. Bruno ◽  
J. A. Whitsett ◽  
A. H. Jobe
Keyword(s):  
Lung Tissue ◽  
Protein A ◽  
Surfactant Protein ◽  
Normal Lung ◽  
Tissue Slices ◽  
Normal Lung Function ◽  
Deficient Mice ◽  
Surfactant Metabolism

In the present study we asked if surfactant metabolism was altered in surfactant protein (SP) A-deficient mice in vivo. Although previous studies in vitro demonstrated that SP-A modulates surfactant secretion and reuptake by type II cells, mice made SP-A deficient by homologous recombination grow and reproduce normally and have normal lung function. Alveolar and lung tissue saturated phophatidylcholine (Sat PC) pools were 50 and 26% larger, respectively, in SP-A(-/-) mice than in SP-A(+/+) mice. Radiolabeled choline and palmitate incorporation into lung Sat PC was similar both in vivo and for lung tissue slices in vitro from SP-A(+/+) and SP-A(-/-) mice. Percent secretion of radiolabeled Sat PC was unchanged from 3 to 15 h, although SP-A(-/-) mice retained more labeled Sat PC in the alveolar lavages at 48 h (consistent with the increased surfactant pool sizes). Clearance of radiolabeled dipalmitoylphosphatidylcholine and SP-B from the air spaces after intratracheal injection was similar in SP-A(-/-) and SP-A(+/+) mice. Lack of SP-A had minimal effects on the overall metabolism of Sat PC or SP-B in mice.

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