Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and beta2-agonist use

• Published in: Respiratory research Vol. 7; p. 25
• Main Authors: Hastie, Annette T, Wu, Min, Foster, Gayle C, Hawkins, Gregory A, Batra, Vikas, Rybinski, Katherine A, Cirelli, Rosemary, Zangrilli, James G, Peters, Stephen P
• Format: Journal Article
• Language: English
• Published: England 15.02.2006
• Subjects: Adrenergic beta-Agonists - administration & dosage; Albuterol - administration & dosage; Asthma - classification; Asthma - metabolism; Bronchodilator Agents - administration & dosage; Cell Adhesion Molecules - metabolism; Humans; Microfilament Proteins - metabolism; Phosphoproteins - metabolism; Phosphorylation - drug effects; Receptors, Adrenergic, beta - metabolism
• ISSN: 1465-993X; 1465-993X
• DOI: 10.1186/1465-9921-7-25

Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this "brake" on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo beta2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for beta2-adrenergic receptor haplotype determination. Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the beta2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to beta-agonist. The decreased phosphorylation does not appear to be associated with a particular beta2-adrenergic receptor haplotype. The observed decrease in VASP phosphorylation suggests greater inhibition of actin reorganization which is necessary for altering attachment and migration required during epithelial repair.