Reduction of tumstatin in asthmatic airways contributes to angiogenesis, inflammation, and hyperresponsiveness

Rationale: Angiogenesis is a prominent feature of remodeling in asthma. Many proangiogenic factors are up-regulated in asthma, but little is known about levels of endogenous antiangiogenic agents. Collagen IV is decreased in the airway basement membrane in asthma. It has six α chains, of which the noncollagenous domain-1 domains have endogenous antiangiogenic properties.Objectives: To study the expression of the noncollagenous domain-1 of the α3 chain of collagen IV, tumstatin, in the airways of subjects with and without asthma and to examine the potential for tumstatin to regulate angiogenesis and inflammation.Methods: We used immunohistochemistry and dot blots to examine the expression of tumstatin in bronchial biopsies, bronchoalveolar lavage fluid, and serum. We then used an in vitro angiogenesis assay and a murine model of allergic airways disease to explore tumstatin's biological function.Measurements and Main Results: The level of tumstatin is decreased 18-fold in the airways of patients with asthm...