Segment‐specific tissue factor expression in mouse lung vasculature

Abstract

In acute lung injury (ALI), pro‐coagulant responses remain undefined in extra‐alveolar versus alveolar vascular segments. Since endothelial vWf content is different in these segments, we considered pro‐coagulant responses might also differ. We determined surface expression of the coagulation initiator, tissue factor (TF) in freshly recovered endothelial cells (FLECs) of acid‐induced mouse lungs. We gave anesthetized mice intra‐nasal HCl (pH 1.2, 2 ml/kg), or buffer. 2 hours later, we perfused the pulmonary artery with chilled EDTA (5mM, 1ml × 5) to obtain vascular cells, which we labeled with vWf or VE‐cadherin, to detect respectively, FLECs from the extra‐alveolar segment alone, or from all segments. We co‐labeled the cells for TF and subjected them to flow cytometry. Acid increased FLEC TF 91±7% above control in vWf+ cells (n=4, P<0.05), but only 42±7% above control in VE‐cadherin+ cells (n=5, P<0.05). In mice treated with anti‐platelet serum, in which platelet counts fell by 86%, the acid‐induced TF increase in vWf+ cells was inhibited by 63±2% (n=4, P<0.05). We conclude, acid‐induced ALI increases lung endothelial TF expression, which is dominant in extra‐alveolar vessels. Further, the TF expression was platelet‐dependent. We propose lung coagulant mechanisms occur mainly in extra‐alveolar vessels (Support: HL036024).