Disulfide bonds and sputum viscoelasticity1

Bornstein, Alan A.; Chen, Tzeng-Ming; Dulfano, Mauricio J.

doi:10.3233/bir-1978-153-413

Cited by 8 publications

(4 citation statements)

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“…In published studies of mucus or sputum rheology, some investigators have measured only static viscosity, 34–42 but in a mucus gel viscosity will vary with the applied stress or the strain rate. Other investigators have measured both static viscosity and elasticity, 43–53 while others (including our group) have evaluated low stress dynamic rheology and measured viscoelasticity and reported this as a function of frequency at 1 and 100 rad/sec 5,27,28,30,54–62 . Because rheological behavior is influenced by polymer structure we have also used LSCM to visualize and measure the length, cross‐linking, density, and interaction among DNA and actin polymers 5…”

Section: Discussionmentioning

confidence: 99%

The Role of DNA and Actin Polymers on the Polymer Structure and Rheology of Cystic Fibrosis Sputum and Depolymerization by Gelsolin or Thymosin Beta 4

Kater

Henke

Rubin

2007

Annals of the New York Academy of Sciences

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Mucus clearance is the first line of pulmonary defense against inhaled irritants, microorganisms, and allergens. In health, the gel-forming mucins are the principal polymeric components of airway mucus but in cystic fibrosis (CF), the necrotic death of inflammatory and epithelial cells releases a network of copolymerized extracellular DNA and filamentous (F-) actin-producing secretions that are similar to pus and difficult to clear by cilia or airflow. The large amounts of F-actin in CF sputum suggested that thymosin beta4 (Tbeta4) or gelsolin could depolymerize the secondary polymer network of CF sputum. Dose-dependent CF sputum rheology and polymer structure were measured before and after the addition of excipient, dornase alfa, Tbeta4, gelsolin, and Tbeta4 or gelsolin with dornase for 30 min. Sputum was also incubated with Tbeta4 30 microg/mL, gelsolin 10 microg/mL or excipient for 0, 5, 10, 15, 20, or 60 min. There was a dose-dependent decrease in cohesivity with Tbeta4 and a time-dependent decrease in cohesivity at 30 microg/mL. With the combination of dornase alfa and Tbeta4 at 1.5 microg/mL, there was a 65% decrease in elasticity (P = 0.013). There was a time-dependent decrease in cohesivity (P = 0.0004) and elasticity (P = 0.047) with gelsolin and a dose-dependent fall in cohesivity (P = 0.0008). An apparent synergy of Tbeta4 or gelsolin on actin and dornase on DNA may be explained by the combined effect of actin depolymerization and DNA filament severing or by virtue of actin depolymerization increasing the effectiveness of dornase alfa.

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Section: Discussionmentioning

confidence: 99%

The Role of DNA and Actin Polymers on the Polymer Structure and Rheology of Cystic Fibrosis Sputum and Depolymerization by Gelsolin or Thymosin Beta 4

Kater

Henke

Rubin

2007

Annals of the New York Academy of Sciences

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“…The finding that the mucin associated DNA is human in origin suggests that it is the inflammatory processes resulting from infection, rather than the infection itself which are the source of the DNA in CF sputum. Hence, if as has been suggested, DNA has a role in establishing the rheological properties of CF sputum [1,6,7), then these properties will, at least in part, be due to inflammatory responses in the lung. To further clarify the importance of these processes it would be of interest to establish what effect the addition of sputum derived DNA has on the viscoelasticity of both purified mucus glycoprotein gels and unpurified sputum.…”

Section: Discussionmentioning

confidence: 90%

“…It has been proposed that DNA may influence the viscoelasticity of sputum [3], presumably through interaction with the major rheological determinants of the secretion, mucus glycoproteins. Attempts to correlate either the degree of purulence or the DNA content with the rheological properties of sputum have led to contradictory results [4][5][6][7]. However, the suggestion is supported by studies indicating that the rheological properties can be reduced by deoxyribonuclease (DNA-ase) treatment [8], and that in vitro addition of DNA to purified [9] and unpurified [1] sputum results in increased viscoelasticity.…”

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confidence: 99%

The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum

Lethem¹,

James²,

Marriott³

et al. 1990

Eur Respir J

190

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The relative importance of host and bacteria-derived deoxyribonucleic acid (DNA) in the increased viscoelasticity of purulent sputum in cystic fibrosis (CF) and other airway diseases is unclear. We report the identification of the DNA associated with mucus glycoproteins purified from the purulent sputum of 9 patients with CF. Mucus glycoproteins were purified from CF sputum by gel exclusion chromatography and the co-purifying DNA isolated by phenol extraction. Electrophoresis indicated that the DNA preparations had a size of approximately 300 to greater than 50,000 bases. The origin of the DNA was determined by slot blotting and subsequent hybridization with 32P-labelled DNA probes specific for human DNA sequences and those from bacterial species commonly isolated from CF sputum. The results indicated that in all cases the DNA was almost entirely human in origin. This implies that it is the patient's own DNA which may contribute to the rheological abnormalities of CF sputum.

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“…11 Sialic acid was estimated by the method of Warren." Sulfhydryl and disulfide content of selected mucins was determined by reductive alkylation with iodacetamide as described by Bornstein et al 13 Rheology. Mucin from each group was reconstituted in a phosphate buffer (pH 7.6) and subjected to intrinsic viscosity determinations via capillary viscometry.…”

Section: Methodsmentioning

confidence: 99%

Human tracheal mucin: A preliminary study of physicochemical properties and mucociliary transport

Wetmore

Brown

Litt

et al. 1983

Otolaryngol.--head neck surg.

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Human tracheal secretions were collected from patients with chronic tracheostomies in the intensive care unit and through an endotracheal tube from pediatric surgical patients under general anesthesia. These secretions were dialyzed, fractionated on an agarose column, and lyophilized to recover the tracheal mucin fraction. Analysis of pooled mucin samples included determination of amino acids, carbohydrates, and sulfates. Intrinsic viscosity, microrheometry, and mucociliary transport studies were also performed. Structural and functional differences between several pools of specimens are cited with an emphasis on possible clinical correlations.

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Disulfide bonds and sputum viscoelasticity1

Cited by 8 publications

References 0 publications

The Role of DNA and Actin Polymers on the Polymer Structure and Rheology of Cystic Fibrosis Sputum and Depolymerization by Gelsolin or Thymosin Beta 4

The Role of DNA and Actin Polymers on the Polymer Structure and Rheology of Cystic Fibrosis Sputum and Depolymerization by Gelsolin or Thymosin Beta 4

The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum

Human tracheal mucin: A preliminary study of physicochemical properties and mucociliary transport

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