Angiopoietin-2 promotes myeloid cell infiltration in a β2-integrin–dependent manner

A Scholz, V Lang, R Henschler… - Blood, The Journal …, 2011 - ashpublications.org
A Scholz, V Lang, R Henschler, M Czabanka, P Vajkoczy, E Chavakis, J Drynski, PN Harter
Blood, The Journal of the American Society of Hematology, 2011ashpublications.org
In human inflammatory diseases, we identified endothelial angiopoietin-2 (Ang-2)
expression to be strongly associated with inflammations mediated by myeloid cells but not
lymphocytes. To identify the underlying mechanism, we made use of a transgenic mouse
model with inducible endothelial cell-specific expression of Ang-2. In this model, in the
absence of inflammatory stimuli, long-term expression of Ang-2 led to a time-dependent
accumulation of myeloid cells in numerous organs, suggesting that Ang-2 is sufficient to …
Abstract
In human inflammatory diseases, we identified endothelial angiopoietin-2 (Ang-2) expression to be strongly associated with inflammations mediated by myeloid cells but not lymphocytes. To identify the underlying mechanism, we made use of a transgenic mouse model with inducible endothelial cell-specific expression of Ang-2. In this model, in the absence of inflammatory stimuli, long-term expression of Ang-2 led to a time-dependent accumulation of myeloid cells in numerous organs, suggesting that Ang-2 is sufficient to recruit myeloid cells. In models of acute inflammation, such as delayed-type hypersensitivity and peritonitis, Ang-2 transgenic animals showed an increased responsiveness. Intravital fluorescence video microscopy revealed augmented cell adhesion as an underlying event. Consequently, we demonstrated that Ang-2 is able to induce strong monocyte adhesion under shear in vitro, which could be blocked by antibodies to β2-integrin. Taken together, our results describe Ang-2 as a novel, endothelial-derived regulator of myeloid cell infiltration that modulates β2-integrin–mediated adhesion in a paracrine manner.
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