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PMN Depletion Alters Ang‐1:Ang‐2 & Increases Tie2 Phosphorylation Following Hemorrhagic Shock Priming for the Development of iARDS in Mice
Author(s) -
LomasNeira Joanne,
Chung ChunShiang,
Ayala Alfred,
Chen Yaping
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.634.5
Subject(s) - angiopoietin receptor , ards , lung , angiopoietin , inflammation , receptor , priming (agriculture) , phosphorylation , stimulation , medicine , endocrinology , immunology , chemistry , biology , vascular endothelial growth factor , biochemistry , vegf receptors , botany , germination
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 PMN depleted mice, undepleted Controls as well as Naive mice and those receiving an Ang‐2 blocking protein. While no statistical change in total Tie2 protein was measured in any of the four groups following ARDS, pTie2 was significantly decreased in lung tissue from mice with PMN (Controls) compared with PMN depleted mice and mice given Ang‐2 blocking protein. pTie2 in lungs of naïve mice was between these 2 groups. This data suggests that while no significant change in Tie2 receptor expression was associated with ARDS in mice, EC/PMN interaction, in addition to altering lung tissue Ang‐2:Ang‐1 ratio, increases pTie2 levels, promoting increased barrier function and decreased lung tissue injury. (NIH GM103652)