Proteomics

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Endothelial Cells from GvsHD Mouse


ABSTRACT: During inflammation immune cells can induce endothelial activation and angiogenesis by cytokines and other mediators1,2. The inhibition of inflammation-associated angiogenesis ameliorates inflammatory diseases by reducing the recruitment of tissue infiltrating leukocytes3-5. However, there is limited evidence on initial mechanisms of both processes. Here we show that angiogenesis precedes leukocyte infiltration during graft-versus-host disease (GVHD) and experimental colitis. A key feature of GVHD is the incompletely understood organ tropism to skin, liver and the intestines. We found that angiogenesis initiates GVHD in target organs whereas in non-target organs no angiogenesis and no subsequent inflammation occur, suggesting a previously unrecognized role of the endothelium in GVHD organ tropism. The initiation phase of angiogenesis was not associated to classical endothelial cell (EC) activation signs, such as Vegfa/VEGFR1+2 upregulation or increased adhesion molecule expression. In gene array- and proteomic analyses, we found significant metabolic and cytoskeleton changes in ECs leading to profoundly higher deformation in real-time deformability cytometry6. Our results demonstrate that metabolic changes trigger enhanced migratory and proliferating potential of ECs during the initiation of angiogenesis in GVHD target organs. Our study adds evidence to the hypothesis that angiogenesis can initiate inflammation and provides novel insight in pathophysiology and tropism of GVHD.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

DISEASE(S): Acute Leukemia

SUBMITTER: Daniel Perez Hernandez  

LAB HEAD: Daniel Perez Hernandez

PROVIDER: PXD004606 | Pride | 2017-01-31

REPOSITORIES: Pride

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Publications


The inhibition of inflammation-associated angiogenesis ameliorates inflammatory diseases by reducing the recruitment of tissue-infiltrating leukocytes. However, it is not known if angiogenesis has an active role during the initiation of inflammation or if it is merely a secondary effect occurring in response to stimuli by tissue-infiltrating leukocytes. Here, we show that angiogenesis precedes leukocyte infiltration in experimental models of inflammatory bowel disease and acute graft-versus-host  ...[more]

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