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Original Research: CYSTIC FIBROSIS |

Thymosin β4 Sequesters Actin in Cystic Fibrosis Sputum and Decreases Sputum Cohesivity in Vitro*

Bruce K. Rubin, MEngr, MD, MBA, FCCP; Arnon P. Kater, MD, PhD; Allan L. Goldstein, PhD
Author and Funding Information

Affiliations: *From the Department of Pediatrics (Drs. Rubin and Kater), Wake Forest University School of Medicine, Winston-Salem, NC; and the Department of Biochemistry and Molecular Biology (Drs. Kater and Goldstein), The George Washington University School of Medicine and Health Sciences, Washington, DC.,  Currently at the Department of Hematology, Academic Medical Center, University of Amsterdam, the Netherlands.

Correspondence to: Bruce K. Rubin, MEngr, MD, MBA, FCCP, Professor and Vice Chair, Department of Pediatrics, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1081; e-mail: brubin@wfubmc.edu



Chest. 2006;130(5):1433-1440. doi:10.1378/chest.130.5.1433
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Background: Filamentous actin (F-actin) forms polymers that contribute to the abnormal biophysical properties of sputum. Thymosin β4 (Tβ4) is the major monomeric actin-sequestering peptide in cells and can depolymerize F-actin. Tβ4 could potentially decrease sputum viscoelasticity and adhesivity and improve sputum clearance.

Methods: Sputum was collected during pulmonary function testing from 17 subjects during a cystic fibrosis (CF) center visit. Sputum rheology, cough and ciliary transportability, and interfacial tension were measured before and after the addition of dornase alfa at 30 μg/mL; Tβ4 at 0.3, 3, 30, and 150 μg/mL; and Tβ4 with dornase alfa at 1.5 μg/mL each. Sputum was separately incubated with Tβ4 at 30 μg/mL for 0, 10, 20, or 60 min.

Results: There was a direct relationship between actin filament length and sputum cohesivity. There was a dose-dependent threshold decrease in cohesivity with Tβ4 and a time-dependent decrease in cohesivity over 60 min at 30 μg/mL. With the combination of dornase alfa and Tβ4 at 1.5 μg/mL each, there was a 70% decrease in G*s and a 65% decrease in G′ at 1 rad/s (p = 0.013). There was a 44% increase in cough transportability of sputum in vitro (p = 0.037) and a 71% increase in mucociliary transportability of sputum in vitro (p = 0.013) relative to control with the combination of dornase alfa and Tβ4, but no significant change with dornase alfa or Tβ4 alone at any concentration.

Conclusions: Actin polymer filament length is correlated with sputum cohesivity. Tβ4 depolymerizes CF sputum actin in both a dose-dependent and a time-dependent manner. An apparent synergy of Tβ4 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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