Biophysical and physiological properties of a modified porcine surfactant enriched with surfactant protein A

Sun, Bo; Curstedt, Tore; Lindgren, Gunnar; Franzén, Bo; Alaiya, Ayodele; Čalkovská, Andrea; Robertson, Bengt

doi:10.1183/09031936.97.10091967

Cited by 41 publications

(27 citation statements)

References 28 publications

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“…The role of SP-A in the resistance to surfactant inhibitors has been demonstrated in previous studies (52). Sun et al (53) reported that in a rat model of MAS, natural porcine surfactant containing 5% SP-A was more effective than the same dose of Curosurf, which contains only polar lipids, SP-B, and SP-C. Addition of SP-A to Curosurf resulted in improved biophysical properties in vitro and better physiologic effects in a rabbit RDS model (53).…”

Section: Discussionmentioning

confidence: 99%

“…Sun et al (53) reported that in a rat model of MAS, natural porcine surfactant containing 5% SP-A was more effective than the same dose of Curosurf, which contains only polar lipids, SP-B, and SP-C. Addition of SP-A to Curosurf resulted in improved biophysical properties in vitro and better physiologic effects in a rabbit RDS model (53). Recently, the possibility that the carbohydrate components of SP-A might be important for resistance to inactivation led Taeusch et al (54) to explore the effects of simple sugars, sugar polymers, and other nonionic polymers on surfactant inactivation by meconium.…”

Section: Discussionmentioning

confidence: 99%

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Resistance of Different Surfactant Preparations to Inactivation by Meconium

et al. 2001

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A disease similar to acute respiratory distress syndrome may occur in neonates after aspiration of meconium. The aim of the study was to compare the inhibitory effects of human meconium on the following surfactant preparations suspended at a concentration of 2.5 mg/mL: Curosurf, Alveofact, Survanta, Exosurf, Pumactant, rabbit natural surfactant from bronchoalveolar lavage, and two synthetic surfactants based on recombinant surfactant protein-C (Venticute) or a leucine/lysine polypeptide. Minimum surface tension, determined with a pulsating bubble surfactometer, was increased Ͼ10 mN/m at meconium concentrations Ն0.04 mg/mL for Curosurf, Alveofact, or Survanta, Ն0.32 mg/mL for recombinant surfactant protein-C, Ն1.25 mg/mL for leucine/lysine polypeptide, and Ն20 mg/mL for rabbit natural surfactant. The protein-free synthetic surfactants Exosurf and Pumactant did not reach minimum surface tension Ͻ10 mN/m even in the absence of meconium. We conclude that surfactant activity is inhibited by meconium in a dose-dependent manner. Recombinant surfactant protein-C and leucine/lysine polypeptide surfactant were more resistant to inhibition than the modified natural surfactants Curosurf, Alveofact, or Survanta but less resistant than natural lavage surfactant containing surfactant protein-A. We speculate that recombinant hydrophobic surfactant proteins or synthetic analogs of these proteins can be used for the design of new surfactant preparations that are relatively resistant to inactivation and therefore suitable for treatment of acute respiratory distress syndrome. Surfactant deficiency has been recognized as the cause of RDS in premature infants, and treatment with modified natural surfactant preparations has considerably improved the prognosis of this disease (1). However, it has been realized that secondary surfactant deficiency caused by inactivation of the surfactant system may occur in patients with mature lungs. In ARDS (acute (adult) RDS), surfactant inhibitors may reach the alveolar space by inhalation or aspiration, and proteins such as albumin or fibrinogen may leak into the airways as a consequence of increased vascular permeability caused by pneumonia, for example (2-4). To treat ARDS in such a patient, relatively large doses of surfactant need to be instilled to overcome the amount of surfactant inhibitors present in the airways (5). Thus, surfactant preparations used for treatment of ARDS should be relatively resistant to inactivation (6). Recent advances in the synthesis and heterologous expression of lung SPs or their analogs might allow the production of designer surfactants (7) that are highly resistant to surfactant inhibitors. Under ARDS-like conditions, such preparations may be superior to currently available modified natural surfactants.Aspiration of meconium can result in severe respiratory failure in term neonates (8 -10). Surfactant inactivation is believed to play a key role in the pathophysiology of MAS, and inhibition of the surface tension-lowering activity of surfactant by meconium has been...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Resistance of Different Surfactant Preparations to Inactivation by Meconium

et al. 2001

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“…Curosurf enriched with 5% SP-A (normally absent in the product) had an increased resistance to inactivation by meconium, fibrinogen, albumin, and serum in vitro and improved pulmonary compliance in immature newborn rabbits after intratracheal instillation of fibrinogen compared with controls treated with only Curosurf (26). In vitro, natural rabbit surfactant (containing about 5% SP-A) was more resistant to inactivation by human meconium than the modified natural surfactants Curosurf, Alveofact, or Survanta (4).…”

Section: Polymyxin B Surfactant and Meconiummentioning

confidence: 99%

Polymyxin B/Pulmonary Surfactant Mixtures Have Increased Resistance to Inactivation by Meconium and Reduce Growth of Gram-Negative Bacteria In Vitro

et al. 2006

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Pulmonary surfactant is inactivated in meconium aspiration syndrome and neonatal pneumonia. Development of an exogenous surfactant less sensitive to inactivation might be useful for treating these diseases. We investigated in vitro whether addition of the cationic cyclic membrane cross-linking peptide polymyxin B (PxB) and/or calcium chloride (CaCl 2 ) to modified porcine surfactant Curosurf increases resistance to meconium-induced inactivation of surface activity while antimicrobial activity of PxB is maintained. To study bacterial proliferation, Escherichia coli, group B streptococci (GBS), or Staphylococcus aureus were incubated 0 -5 h in saline or in meconium in the presence or absence of Curosurf with or without PxB. PxB and CaCl 2 improved spreading and adsorption of Curosurf. Curosurf plus CaCl 2 /PxB needed a 4-fold increase of meconium concentration to increase dynamic surface tension significantly compared with Curosurf plus CaCl 2 alone, indicating that PxB further increases the resistance of Curosurf to meconium-induced inactivation. Meconium alone like meconium/Curosurf promoted growth of E. coli and GBS, but addition of Curosurf/PxB or PxB alone significantly reduced the growth of E. coli. Biophysical and antibacterial properties of Curosurf and PxB may be combined into a useful adjunct in the treatment of neonatal Gram-negative pneumonia and/or meconium aspiration syndrome.

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“…Firstly, the use of natural surfactants leads to an improved disease outcome, compared with that obtained with synthetic surfactants (14). Secondly, the enrichment of extracted porcine surfactant with SP-A 4 has been shown to prevent inactivation of surfactant function by serum proteins (15). To further understand the surfactant protein components and to initiate research into the protective benefits of surfactant protein in surfactant preparations, the cDNA for porcine SP-D was cloned.…”

mentioning

confidence: 99%

Porcine Lung Surfactant Protein D: Complementary DNA Cloning, Chromosomal Localization, and Tissue Distribution

Eijk

Haagsman

Skinner

et al. 2000

The Journal of Immunology

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Porcine organs and lung surfactant have medically important applications in both xenotransplantation and therapy. We have started to characterize porcine lung surfactant by cloning the cDNA of porcine surfactant protein D (SP-D). SP-D and SP-A are important mediators in innate immune defense for the lung and possibly other mucosal surfaces. Porcine SP-D will also be an important reagent for use in existing porcine animal models for human lung infections. The complete cDNA sequence of porcine SP-D, including the 5′ and 3′ untranslated regions, was determined from two overlapping bacteriophage clones and by PCR cloning. Three unique features were revealed from the porcine sequence in comparison to SP-D from other previously characterized species, making porcine SP-D an intriguing species addition to the SP-D/collectin family. The collagen region contains an extra cysteine residue, which may have important structural consequences. The other two differences, a potential glycosylation site and an insertion of three amino acids, lie in the loop regions of the carbohydrate recognition domain, close to the carbohydrate binding region and thus may have functional implications. These variations were ruled out as polymorphisms or mutations by confirming the sequence at the genomic level in four different pig breeds. Porcine SP-D was shown to localize primarily to the lung and with less abundance to the duodenum, jejunum, and ileum. The genes for SP-D and SP-A were also shown to colocalize to a region of porcine chromosome 14 that is syntenic with the human and murine collectin loci.

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Biophysical and physiological properties of a modified porcine surfactant enriched with surfactant protein A

Cited by 41 publications

References 28 publications

Resistance of Different Surfactant Preparations to Inactivation by Meconium

Resistance of Different Surfactant Preparations to Inactivation by Meconium

Polymyxin B/Pulmonary Surfactant Mixtures Have Increased Resistance to Inactivation by Meconium and Reduce Growth of Gram-Negative Bacteria In Vitro

Porcine Lung Surfactant Protein D: Complementary DNA Cloning, Chromosomal Localization, and Tissue Distribution

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