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Blood, 20 August 2009, Vol. 114, No. 8, pp. 1696-1706. Prepublished online as a Blood First Edition Paper on June 22, 2009; DOI 10.1182/blood-2008-11-187682. This Article Full Text Full Text (PDF) Supplemental Methods, Figures, and Videos All Versions of this Article: blood-2008-11-187682v1 114/8/1696    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Kneilling, M. Articles by Röcken, M. PubMed PubMed Citation Articles by Kneilling, M. Articles by Röcken, M. Related Collections Immunobiology Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY Direct crosstalk between mast cell–TNF and TNFR1-expressing endothelia mediates local tissue inflammation Manfred Kneilling1, Reinhard Mailhammer2, Lothar Hültner2, Tanja Schönberger3, Kerstin Fuchs1, Martin Schaller1, Daniel Bukala4, Steffen Massberg5, Christian A. Sander6, Heidi Braumüller1, Martin Eichner7, Konrad L. Maier8, Rupert Hallmann9, Bernd J. Pichler4, Roland Haubner10, Meinrad Gawaz3, Klaus Pfeffer11, Tilo Biedermann1, and Martin Röcken1 1 Department of Dermatology, Eberhard Karls University, Tübingen, Germany; 2 Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany; 3 Department of Medicine III, Eberhard Karls University, Tübingen, Germany; 4 Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens Foundation, Department of Radiology, Eberhard Karls University, Tübingen, Germany; 5 Department of Medicine and Deutsches Herzzentrum, Technische Universität München, Munich, Germany; 6 Department of Dermatology, St Georg Hospital, Hamburg, Germany; 7 Department of Medical Biometry, Eberhard Karls University, Tübingen, Germany; 8 Institute of Inhalation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany; 9 Institute for Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; 10 Department of Nuclear Medicine, University of Innsbruck, Innsbruck, Austria; and 11 Department of Microbiology, University of Düsseldorf, Düsseldorf, Germany Signaling through tumor necrosis factor receptor 1 (TNFR1) controls bacterial infections and the induction of inflammatory Th1 cell–mediated autoimmune diseases. By dissecting Th1 cell–mediated delayed-type hypersensitivity responses (DTHRs) into single steps, we localized a central defect to the missing TNFR1 expression by endothelial cells (ECs). Adoptive transfer and mast cell knockin experiments into KitW/KitW-v, TNF–/–, and TNFR1–/– mice showed that the signaling defect exclusively affects mast cell–EC interactions but not T cells or antigen-presenting cells. As a consequence, TNFR1–/– mice had strongly reduced mRNA and protein expression of P-selectin, E-selectin, ICAM-1, and VCAM-1 during DTHR elicitation. In consequence, intravital fluorescence microscopy revealed up to 80% reduction of leukocyte rolling and firm adhesion in TNFR1–/– mice. As substitution of TNF–/– mice with TNF-producing mast cells fully restored DTHR in these mice, signaling of mast cell-derived TNF through TNFR1-expressing ECs is essential for the recruitment of leukocytes into sites of inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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