Angiopoietin-2-Driven Vascular Remodeling in Airway Inflammation

Vascular remodeling is a feature of chronic inflammation during which capillaries transform into venules that expand the region of the vasculature in which leakage and leukocyte emigration both occur Recently we found that angiopoietin/Tie2 receptor signaling drives the transformation of capillaries into venules at an early stage of the sustained inflammatory response m the airways of mice infected with Mycoplasma put moms However the precise contributions of both angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2) are not clear In this study we sought to determine the contribution of Ang2 to this vascular remodeling Ang2 mRNA expression levels increased and phosphorylated Tie2 immunoreactivity m mucosal blood vessels decreased indicative of diminished receptor signaling after infection Selective inhibition of Ang2 throughout the infection by administration of either of two distinct function blocking antibodies reduced the suppression of Tie2 phosphorylation and decreased the remodeling of mucosal capillaries into venules the amount of leukocyte influx and disease severity These findings are consistent with Ang2 acting as an antagonist of Tie2 receptors and the reduction of Tie2 phosphorylation in endothelial cells rendering the vasculature more responsive to cytokines that promote both vascular remodeling and the consequences of inflammation after M pul moms infection By blocking such changes Ang2 in hibitors may prove beneficial in the treatment of sus tamed inflammation in which vascular remodeling leakage and leukocyte influx contribute to its pathophysiology (Am J Pathol 2010 1773233-3244, DOI 10 2353/ajpath 2010 100059)