Cultured lung fibroblasts from ovalbumin-challenged "asthmatic" mice differ functionally from normal

Area of Science:

• Immunology
• Cell Biology
• Pulmonary Medicine

Background:

• Asthmatic airway remodeling involves goblet cell hyperplasia, angiogenesis, smooth muscle hypertrophy, and subepithelial fibrosis.
• The role of acquired fibroblast phenotype changes in contributing to airway remodeling remains to be fully elucidated.

Purpose of the Study:

• To investigate whether acquired changes in fibroblast phenotype contribute to airway remodeling in asthma.
• To assess functional differences in airway and parenchymal fibroblasts from control and ovalbumin (OVA)-challenged asthmatic mice.

Main Methods:

• Fibroblasts were isolated from control and chronically OVA-sensitized and challenged
• asthmatic
• mice.
• Assessed functions included gel contraction, chemotaxis, mediator release (TGF-beta(1), fibronectin, VEGF), alpha-smooth muscle actin expression, and proliferation.
• Fibroblast responses to exogenous transforming growth factor (TGF)-beta(1) were also evaluated.

Main Results:

• OVA-challenged mouse fibroblasts exhibited augmented gel contraction and chemotaxis.
• Increased release of TGF-beta(1), fibronectin, and vascular endothelial growth factor (VEGF) was observed in asthmatic fibroblasts.
• Asthmatic fibroblasts expressed more alpha-smooth muscle actin, and parenchymal fibroblasts showed increased proliferation compared to controls. TGF-beta(1) stimulation did not abrogate these differences.

Conclusions:

• In this asthma model, OVA-challenged mouse fibroblasts acquire a distinct phenotype.
• The augmented profibrotic activity and mediator release of these asthmatic fibroblasts suggest a contribution to airway remodeling in asthma.