PMN Depletion Alters Ang‐1:Ang‐2 & Increases Tie2 Phosphorylation Following Hemorrhagic Shock Priming for the Development of iARDS in Mice

TL;DRAbstract

Successful therapies for acute respiratory distress syndrome(ARDS) remain challenging. We have recently shown, in our mouse model of hemorrhage priming (Hem) for the development of ARDS following subsequent septic challenge, that depletion of peripheral blood neutrophils(PMN), prior to Hem, reduces lung inflammation/tissue injury and alters ratio of endothelial cell(EC) growth factors, Angiopoietin(Ang)‐1&2. Ang1&2 modulate EC activation, competing for a shared receptor, Tie2, constitutively expressed on ECs. Ang‐1, released by pericytes, promotes an anti‐inflammatory/pro‐survival and Tie2 phosphorylation, while Ang‐2, stored preformed and released from activated ECs, promotes decreased barrier function/increased lung permeability and inhibits pTie2. In PMN depleted ARDS mice, plasma and lung tissue Ang‐2 is significantly decreased. To understand how this relates to reduced lung tissue injury we assessed changes in phopho‐(p)Tie2 vs. total Tie2 expression in lung tissue from PM

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