Tumor necrosis factor α (TNF-α) receptor-II is required for TNF-α–induced leukocyte-endothelial interaction in vivo
| Autor: | Murat Unsal, Lin Yang, Earl Poptic, Justin Bohn, Kagan Ozer, Maria Siemionow, Zhongmin Zhou, Paul E. DiCorleto, Philip H. Howe, Unni M. Chandrasekharan, Marc Penn |
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| Rok vydání: | 2006 |
| Předmět: |
musculoskeletal diseases
biology Cell adhesion molecule Leukocyte adhesion molecule Immunology Intercellular Adhesion Molecule-1 Soluble cell adhesion molecules hemic and immune systems Leukocyte Rolling Cell Biology Hematology Adhesion Biochemistry biological factors Cell biology nervous system E-selectin biology.protein Cell adhesion |
| Zdroj: | Blood. 109:1938-1944 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Tumor necrosis factor-α (TNF-α) binds to 2 distinct cell-surface receptors: TNF-α receptor-I (TNFR-I: p55) and TNF-α receptor-II (TNFR-II: p75). TNF-α induces leukocyte adhesion molecules on endothelial cells (ECs), which mediate 3 defined steps of the inflammatory response; namely, leukocyte rolling, firm adhesion, and transmigration. In this study, we have investigated the role of p75 in TNF-α–induced leukocyte adhesion molecules using cultured ECs derived from wild-type (WT), p75-null (p75−/−), or p55-null (p55−/−) mice. We observed that p75 was essential for TNF-α–induced E-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) expression. We also investigated the putative role of p75 in inflammation in vivo using an intravital microscopic approach with a mouse cremaster muscle model. TNF-α–stimulated leukocyte rolling, firm adhesion to ECs, and transmigration were dramatically reduced in p75−/− mice. Transplanted WT cremaster in p75−/− mice showed a robust leukocyte rolling and firm adhesion upon TNF-α activation, suggesting that the impairment in EC-leukocyte interaction in p75−/− mice is due to EC dysfunction. These results demonstrate, for the first time, that endothelial p75 is essential for TNF-α–induced leukocyte–endothelial-cell interaction. Our findings may contribute to the identification of novel p75-targeted therapeutic approaches for inflammatory diseases. |
| Databáze: | OpenAIRE |
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