Mast Cells Increase Vascular Permeability by Heparin-Initiated Bradykinin Formation In Vivo
| Autor: | Reinhard Sedlmeier, Jenny Björkqvist, Peter Burfeind, Thomas Tradler, Werner Müller-Esterl, Walter A. Wuillemin, Bernd Lecher, Thomas Renné, Chris Oschatz, Gunnar Nilsson, Sven Hammerschmidt, Thomas Jansen, Coen Maas, Sven Cichon |
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| Jazyk: | angličtina |
| Předmět: |
Male
Kallikrein-Kinin System Vascular permeability 030204 cardiovascular system & hematology Pharmacology Mice Plasma chemistry.chemical_compound 0302 clinical medicine Edema Leukocytes Immunology and Allergy Mast Cells Skin 0303 health sciences Factor XII Passive Cutaneous Anaphylaxis Heparin Kinin Extravasation 3. Good health Infectious Diseases Hereditary angioedema Hypotension medicine.symptom Complement C1 Inhibitor Protein Signal Transduction medicine.drug Immunology Bradykinin Biology Capillary Permeability 03 medical and health sciences Paracrine Communication Cell Adhesion medicine Animals 030304 developmental biology Endothelial Cells Immunoglobulin E medicine.disease Rats Enzyme Activation chemistry Capillary Leak Syndrome |
| Zdroj: | Immunity. (2):258-268 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2011.02.008 |
| Popis: | SummaryActivated mast cells trigger edema in allergic and inflammatory disease. We report a paracrine mechanism by which mast cell-released heparin increases vascular permeability in vivo. Heparin activated the protease factor XII, which initiates bradykinin formation in plasma. Targeting factor XII or kinin B2 receptors abolished heparin-triggered leukocyte-endothelium adhesion and interfered with a mast cell-driven drop in blood pressure in rodents. Intravital laser scanning microscopy and tracer measurements showed heparin-driven fluid extravasation in mouse skin microvessels. Ablation of factor XII or kinin B2 receptors abolished heparin-induced skin edema and protected mice from allergen-activated mast cell-driven leakage. In contrast, heparin and activated mast cells induced excessive edema in mice deficient in the major inhibitor of factor XII, C1 esterase inhibitor. Allergen exposure triggered edema attacks in hereditary angioedema patients, lacking C1 esterase inhibitor. The data indicate that heparin-initiated bradykinin formation plays a fundamental role in mast cell-mediated diseases. |
| Databáze: | OpenAIRE |
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