Shear stress-mediated F1/FO ATP synthase-dependent CO2 gas excretion from human pulmonary arteriolar endothelial cells.

We studied the physiological role of flow through pulmonary arterioles in CO(2) gas exchange. We established human pulmonary arteriolar endothelial cells (HPAoEC). The cells demonstrated marked immunocytochemical staining of PECAM-1, VEGF R2, ACE-1, and CA type IV on their cell surface. Ten seconds shear stress stimulation caused the co-release of H(+) and ATP via the activation of F(1)/F(O) ATP synthase on the HPAoEC. F(1)/F(O) ATP synthase was immunocytochemically observed on the cell surface of non-permeabilized HPAoEC. In the shear stress-loaded HPAoEC culture media supernatant, ATPase activity increased in a time-dependent manner. The HPAoEC were strongly stained for NTPDase 1, which partially co-localized with purinergic P2Y1. The purinergic P2Y1 receptor agonist UTP (10(-6) M) significantly potentiated the shear stress-induced increase in ATPase activity in the culture medium supernatant. Ten seconds shear stress stimulation also produced stress strength-dependent CO(2) gas excretion from the HPAoEC, which was significantly reduced by the inhibition of F(1)/F(O) ATP synthase or CA IV on the endothelial cell (EC) surface. In conclusion, we have proposed a new concept of CO(2) exchange in the human lung, flow-mediated F(1)/F(O) ATP synthase-dependent H(+) secretion, resulting in the facilitation of a dehydration reaction involving HCO3(-) in plasma and the excretion of CO(2) gas from arteriolar ECs.