Dataset Information

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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Dataset's files

Source:

			Action	DRS
	AllPeptides.txt	Txt
	RAW.raw	Raw
	proteinGroups.txt	Txt

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Publications

Initiation of acute graft-versus-host disease by angiogenesis.

Riesner Katarina K Shi Yu Y Jacobi Angela A Kräter Martin M Kalupa Martina M McGearey Aleixandria A Mertlitz Sarah S Cordes Steffen S Schrezenmeier Jens-Florian JF Mengwasser Jörg J Westphal Sabine S Perez-Hernandez Daniel D Perez-Hernandez Daniel D Schmitt Clemens C Dittmar Gunnar G Guck Jochen J Penack Olaf O

Blood 20170117 14

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]

PMID: 28096092

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Project description:During inflammatory diseases, infiltrating immune cells can induce endothelial activation and angiogenesis by cytokines and other mediators. The inhibition of inflammation-associated angiogenesis ameliorates inflammatory diseases by reducing the recruitment of tissue infiltrating leukocytes. However, there is limited evidence on initial mechanisms of both processes. We show in experimental models that angiogenesis precedes leukocyte infiltration during graft-versus-host disease (GVHD). GVHD, a systemic inflammatory disease caused by host-reactive T cells primarily attacking the epithelial cells of the GVHD target organs liver, skin and intestines, leads to substantial morbidity and mortality after allogeneic hematopoetic stem cell transplantation. A key feature of GVHD is the incompletely understood organ tropism to skin, liver and the intestines. We demonstrate that angiogenesis initiates GVHD in target organs whereas in non-target organs no angiogenesis and no subsequent inflammation occurred. To shed light into the initiation phase of angiogenesis we looked at classical endothelial cell activation signs, such as upregulation of the Vegfa/VEGFR1+2 pathway or adhesion molecules, but could not find an association. However, endothelial cells in early GVHD showed profoundly higher deformation in real-time deformability cytometry suggesting enhanced migratory and proliferating potential of endothelial cells during the initiation of angiogenesis in GVHD target organs. We used microarrays to detect alternative pathways in endothelial cells of the GVHD target organ colon that could be responisble for initial angiogenesis in GVHD. We identified several up-and down-regulated genes during this process. Strikingly, we found several cytoskeleton as well as metabolic-associated and related gene alterations which may explain the enhanced migration and proliferation of endothelial cells in initiating GVHD. Our study adds evidence to the hypothesis that angiogenesis can initiate inflammation and provides novel insight in pathophysiology and tropism of GVHD.