دورية أكاديمية
VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration.
| العنوان: | VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration. |
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| المؤلفون: | van Wetering S; Department of Experimental Immunohematology, Sanquin Research at CLB, 1066 CX Amsterdam, The Netherlands., van den Berk N, van Buul JD, Mul FP, Lommerse I, Mous R, ten Klooster JP, Zwaginga JJ, Hordijk PL |
| المصدر: | American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2003 Aug; Vol. 285 (2), pp. C343-52. Date of Electronic Publication: 2003 Apr 16. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901225 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0363-6143 (Print) Linking ISSN: 03636143 NLM ISO Abbreviation: Am J Physiol Cell Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society, |
| مواضيع طبية MeSH: | Cell Adhesion/*physiology , Cell Communication/*physiology , Chemotaxis, Leukocyte/*physiology , Endothelium, Vascular/*metabolism , Leukocytes/*metabolism , Vascular Cell Adhesion Molecule-1/*metabolism , rac GTP-Binding Proteins/*metabolism, ADP Ribose Transferases/pharmacology ; Botulinum Toxins/pharmacology ; Cell Adhesion/drug effects ; Cell Communication/drug effects ; Cell Line ; Chemotaxis, Leukocyte/drug effects ; Endothelium, Vascular/cytology ; Endothelium, Vascular/drug effects ; Enzyme Inhibitors/pharmacology ; Humans ; Interleukin-1/pharmacology ; Leukocytes/cytology ; Leukocytes/drug effects ; Mitogen-Activated Protein Kinases/drug effects ; Mitogen-Activated Protein Kinases/metabolism ; Peptide Fragments/pharmacology ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Vascular Cell Adhesion Molecule-1/drug effects ; p38 Mitogen-Activated Protein Kinases ; rac GTP-Binding Proteins/drug effects ; rhoA GTP-Binding Protein/drug effects ; rhoA GTP-Binding Protein/metabolism |
| مستخلص: | Leukocyte adhesion is mediated totally and transendothelial migration partially by heterotypic interactions between the beta1- and beta2-integrins on the leukocytes and their ligands, Ig-like cell adhesion molecules (Ig-CAM), VCAM-1, and ICAM-1, on the endothelium. Both integrins and Ig-CAMs are known to have signaling capacities. In this study we analyzed the role of VCAM-1-mediated signaling in the control of endothelial cell-cell adhesion and leukocyte transendothelial migration. Antibody-mediated cross-linking of VCAM-1 on IL-1beta-activated primary human umbilical vein endothelial cells (pHUVEC) induced actin stress fiber formation, contractility, and intercellular gaps. The effects induced by VCAM-1 cross-linking were inhibited by C3 toxin, indicating that the small GTPase p21Rho is involved. In addition, the effects of VCAM-1 were accompanied by activation of Rac, which we recently showed induce intercellular gaps in pHUVEC in a Rho-dependent fashion. With the use of a cell-permeable peptide inhibitor, it was shown that Rac signaling is required for VCAM-1-mediated loss of cell-cell adhesion. Furthermore, VCAM-1-mediated signaling toward cell-cell junctions was accompanied by, and dependent on, Rac-mediated production of reactive oxygen species and activation of p38 MAPK. In addition, it was found that inhibition of Rac-mediated signaling blocks transendothelial migration of monocytic U937 cells. Together, these data indicate that VCAM-1-induced, Rac-dependent signaling plays a key role in the modulation of vascular-endothelial cadherin-mediated endothelial cell-cell adhesion and leukocyte extravasation. |
| التعليقات: | Comment in: Am J Physiol Cell Physiol. 2003 Aug;285(2):C250-2. (PMID: 12842833) |
| المشرفين على المادة: | 0 (Enzyme Inhibitors) 0 (Interleukin-1) 0 (Peptide Fragments) 0 (Reactive Oxygen Species) 0 (Vascular Cell Adhesion Molecule-1) EC 2.4.2.- (ADP Ribose Transferases) EC 2.4.2.- (exoenzyme C3, Clostridium botulinum) EC 2.7.11.24 (Mitogen-Activated Protein Kinases) EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) EC 3.4.24.69 (Botulinum Toxins) EC 3.6.5.2 (rac GTP-Binding Proteins) EC 3.6.5.2 (rhoA GTP-Binding Protein) |
| تواريخ الأحداث: | Date Created: 20030418 Date Completed: 20030905 Latest Revision: 20220227 |
| رمز التحديث: | 20240627 |
| DOI: | 10.1152/ajpcell.00048.2003 |
| PMID: | 12700137 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0363-6143 |
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| DOI: | 10.1152/ajpcell.00048.2003 |