Lung homing of endothelial progenitor cells in humans with asthma after allergen challenge

Rationale: Increasedbronchial vascularity isafeatureof asthmathat can contribute to airflow obstruction andprogressivedecline in lungfunction. Angiogenesis is associated with the lung homing and in situ differentiation of endothelial progenitor cells (EPC) in mouse models of asthma. We have previously shown that inhibiting allergen (Ag)-induced recruitment of EPC in sensitized mice attenuated increased bronchial vascularity anddevelopment of airwayhyperresponsiveness. Objectives: We investigated the accumulation of EPC and formation of new blood vessels in the lungs of human subjects with asthma after Ag inhalation challenge. Methods: Consenting patients with mild atopic asthma (n = 13) with FEV 1≥70%, methacholine PC 20≤16 mg/ml, and a dual response to Ag were recruited. Sputum levels of EPC were determined by multigating flow cytometry, and lung vascularity was enumerated by immunostaining with von Willebrand factor. Measurements and Main Results: Sputum levels of EPC were determined by multigating flow cytometry and lung vascularity was enumerated by immunostaining with von Willebrand factor. There was a significant increase in sputum EPC levels 24 hours post Ag but not diluent challenge. Similarly, a significant increase in the number and diameter of blood vessels in lung biopsy tissue 24 hours post Ag was observed. In vitro culture of EPC demonstrated the capacity of these cells to differentiate into mature endothelial cells and form tubelike vessel structures. In sputum supernatants, there was a significant increase inCXCR2agonists, IL-8,andGro-α 24 hours post Ag. Only Gro-α stimulated a significant EPCmigrational response in vitro. Conclusions: Our data suggest that increased lung homing of EPC may promote bronchial vascularity in allergic asthmatic responses and that the recruitment of these progenitors maybe orchestrated by CXCR2 chemokines.