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

Autor:	Riesner K; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany., Shi Y; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany., Jacobi A; Biotechnology Center, and., Kräter M; University Clinic Carl Gustav Carus Dresden, Medical Clinic and Polyclinic 1, Technical University Dresden, Dresden, Germany; and., Kalupa M; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany., McGearey A; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany., Mertlitz S; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany., Cordes S; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany., Schrezenmeier JF; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany.; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany., Mengwasser J; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany., Westphal S; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany., Perez-Hernandez D; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany., Schmitt C; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany.; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany., Dittmar G; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany., Guck J; Biotechnology Center, and., Penack O; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2017 Apr 06; Vol. 129 (14), pp. 2021-2032. Date of Electronic Publication: 2017 Jan 17.
DOI:	10.1182/blood-2016-08-736314
Abstrakt:	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 disease (GVHD). We found that angiogenesis occurred as early as day+2 after allogeneic transplantation mainly in GVHD typical target organs skin, liver, and intestines, whereas no angiogenic changes appeared due to conditioning or syngeneic transplantation. The initiation phase of angiogenesis was not associated with classical endothelial cell (EC) activation signs, such as Vegfa / VEGFR1+2 upregulation or increased adhesion molecule expression. During early GVHD at day+2, we found significant metabolic and cytoskeleton changes in target organ ECs in gene array and proteomic analyses. These modifications have significant functional consequences as indicated by profoundly higher deformation in real-time deformability cytometry. Our results demonstrate that metabolic changes trigger alterations in cell mechanics, leading to enhanced migratory and proliferative potential of ECs during the initiation of inflammation. Our study adds evidence to the hypothesis that angiogenesis is involved in the initiation of tissue inflammation during GVHD. (© 2017 by The American Society of Hematology.)
Databáze:	MEDLINE
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