دورية أكاديمية
Activation of endothelial extracellular signal-regulated kinase is essential for neutrophil transmigration: Potential involvement of a soluble neutrophil factor in endothelial activation
العنوان: | Activation of endothelial extracellular signal-regulated kinase is essential for neutrophil transmigration: Potential involvement of a soluble neutrophil factor in endothelial activation |
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المؤلفون: | Stein, B., Gamble, J., Pitson, S., Vadas, M., Khew-Goodall, Y. |
المصدر: | http://dx.doi.org/10.4049/jimmunol.171.11.6097Test. |
بيانات النشر: | Amer Assoc Immunologists |
سنة النشر: | 2003 |
المجموعة: | The University of Adelaide: Digital Library |
مصطلحات موضوعية: | Endothelium, Vascular, Neutrophils, Cells, Cultured, Humans, Flavonoids, MAP Kinase Kinase Kinases, MAP Kinase Kinase Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Antibodies, Blocking, Enzyme Inhibitors, Culture Media, Conditioned, Cell Migration Inhibition, Cell Adhesion, Chemotaxis, Leukocyte, Neutrophil Activation, Neutrophil Infiltration, Enzyme Activation, Molecular Weight, Solubility, CD18 Antigens |
الوصف: | During an inflammatory response induced by infection or injury, leukocytes traverse the endothelial barrier into the tissue space. Extravasation of leukocytes is a multistep process involving rolling, tethering, firm adhesion to the endothelium, and finally, transendothelial migration, the least characterized step in the process. The resting endothelium is normally impermeable to leukocytes; thus, during inflammation, intracellular signals that modulate endothelial permeability are activated to facilitate the paracellular passage of leukocytes. Using a static in vitro assay of neutrophil transmigration across human umbilical vein endothelium, a panel of inhibitors of intracellular signaling was screened for their ability to inhibit transmigration. PD98059, a specific inhibitor of extracellular signal-regulated kinase (ERK) 1/2 activation, inhibited both transmigration across TNF-alpha-activated endothelium and transmigration induced by the chemoattractant fMLP in a dose-dependent manner. PD98059 did not inhibit neutrophil chemotaxis in the absence of an endothelial barrier nor neutrophil adhesion to the endothelium, suggesting that its effect was on the endothelium, and furthermore, that endothelial ERK activation may be important for transmigration. We demonstrate in this study that endothelial ERK is indeed activated during neutrophil transmigration and that its activation is dependent on the addition of neutrophils to the endothelium. Further characterization showed that the trigger for endothelial ERK activation is a soluble protein of molecular mass approximately 30 kDa released from neutrophils after activation. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 0022-1767 1550-6606 |
العلاقة: | Journal of Immunology, 2003; 171(11):6097-6104; http://hdl.handle.net/2440/9608Test; Stein, B. [0000-0002-9562-6326]; Pitson, S. [0000-0002-9527-2740]; Khew-Goodall, Y. [0000-0002-0473-5392] |
DOI: | 10.4049/jimmunol.171.11.6097 |
الإتاحة: | https://doi.org/10.4049/jimmunol.171.11.6097Test http://hdl.handle.net/2440/9608Test |
رقم الانضمام: | edsbas.3CB11FB9 |
قاعدة البيانات: | BASE |
تدمد: | 00221767 15506606 |
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DOI: | 10.4049/jimmunol.171.11.6097 |