Granzyme B Promotes Cytotoxic Lymphocyte Transmigration via Basement Membrane Remodeling
| Autor: | Paulus Mrass, Stephen J. Turner, Bosco K. Ho, Marcia A. Munoz, Matthew R. Olson, Philip L. Tong, Monica Devi Prakash, Aulikki Koskinen, Phillip I. Bird, Rohit Jain, Oded Kleifeld, Wolfgang Weninger, Matthias Regner |
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| Rok vydání: | 2014 |
| Předmět: |
Ectromelia virus
Lymphocyte Immunology Basement Membrane Granzymes GZMB Extracellular matrix Mice 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Animals Immunology and Allergy Cytotoxic T cell Ectromelia Infectious Cells Cultured 030304 developmental biology Mice Knockout Basement membrane Extracellular Matrix Proteins 0303 health sciences biology Transendothelial and Transepithelial Migration biology.organism_classification Cell biology Killer Cells Natural Mice Inbred C57BL Granzyme B Infectious Diseases medicine.anatomical_structure Granzyme 030220 oncology & carcinogenesis Proteolysis biology.protein Chemokines T-Lymphocytes Cytotoxic |
| Zdroj: | Immunity. 41:960-972 |
| ISSN: | 1074-7613 |
| Popis: | SummaryGranzyme B (GzmB) is a protease with a well-characterized intracellular role in targeted destruction of compromised cells by cytotoxic lymphocytes. However, GzmB also cleaves extracellular matrix components, suggesting that it influences the interplay between cytotoxic lymphocytes and their environment. Here, we show that GzmB-null effector T cells and natural killer (NK) cells exhibited a cell-autonomous homing deficit in mouse models of inflammation and Ectromelia virus infection. Intravital imaging of effector T cells in inflamed cremaster muscle venules revealed that GzmB-null cells adhered normally to the vessel wall and could extend lamellipodia through it but did not cross it efficiently. In vitro migration assays showed that active GzmB was released from migrating cytotoxic lymphocytes and enabled chemokine-driven movement through basement membranes. Finally, proteomic analysis demonstrated that GzmB cleaved basement membrane constituents. Our results highlight an important role for GzmB in expediting cytotoxic lymphocyte diapedesis via basement membrane remodeling. |
| Databáze: | OpenAIRE |
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