GPVI and Thromboxane Receptor on Platelets Promote Proinflammatory Macrophage Phenotypes during Cutaneous Inflammation
Autor: | Stefanie Frölich, Gerd Geisslinger, Sascha Meyer dos Santos, Nerea Ferreirós, Dominique Thomas, Bona Linke, Domenico Del Turco, Neda Tarighi, Klaus Scholich, Jing Suo, Marco Sisignano, Thomas Deller, Rolf M. Nüsing, Bernhard Nieswandt, Sandra Pierre, Natasja deBruin, David Stegner |
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Rok vydání: | 2017 |
Předmět: |
Blood Platelets
Male 0301 basic medicine Thromboxane Receptors Cell Surface Inflammation Platelet Membrane Glycoproteins Dermatology Biology Biochemistry Receptors Thromboxane A2 Prostaglandin H2 Proinflammatory cytokine Collagen receptor Thromboxane receptor Mice Thromboxane A2 03 medical and health sciences chemistry.chemical_compound medicine Animals Macrophage Lectins C-Type Molecular Biology Skin Macrophages Cell Biology Cell biology Mice Inbred C57BL Mannose-Binding Lectins Phenotype 030104 developmental biology chemistry Immunology Female Collagen GPVI medicine.symptom Gene Deletion Mannose Receptor |
Zdroj: | Journal of Investigative Dermatology. 137:686-695 |
ISSN: | 0022-202X |
Popis: | Platelets are well known for their role in hemostasis but are also increasingly recognized for their supporting role in innate immune responses. Here, we studied the role of platelets in the development of peripheral inflammation and found that platelets colocalize with macrophages in the inflamed tissue outside of blood vessels in different animal models for cutaneous inflammation. Collagen-treatment of macrophages isolated from paws during zymosan-induced inflammation induced thromboxane synthesis through the platelet-expressed collagen receptor glycoprotein VI. Deletion of glycoprotein VI or its downstream effector thromboxane A2 receptor (TP) reduced zymosan-induced mechanical allodynia without altering macrophage recruitment or formation of macrophage/platelet complexes. Instead, macrophages in inflamed paws of glycoprotein VI- and TP-deficient mice exhibited an increased expression of anti-inflammatory markers and synthesized less proinflammatory mediators (prostaglandin E2 and IL6). TP expression on platelets was necessary to mediate increased prostaglandin E2 and IL6 synthesis, whereas TP expression on macrophages was sufficient to decrease the expression of the anti-inflammatory macrophage marker CD206, showing that TP activation on platelets and macrophages regulates different aspects of macrophage activation. |
Databáze: | OpenAIRE |
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