Neointimal Smooth Muscle Cells Display a Proinflammatory Phenotype Resulting in Increased Leukocyte Recruitment Mediated by P-Selectin and Chemokines
| Autor: | Wolfgang Erl, Christian Weber, Ute Zeiffer, Elisa A. Liehn, Andreas Schober, Michael Lietz, Neil Emans, Zhong-qun Yan |
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| Rok vydání: | 2004 |
| Předmět: |
Chemokine
Arteriosclerosis Physiology Aorta Thoracic Constriction Pathologic Integrin alpha4beta1 Monocytes Muscle Smooth Vascular Receptors Interleukin-8B Rats Sprague-Dawley Mice NF-KappaB Inhibitor alpha Recurrence T-Lymphocyte Subsets Cells Cultured Mice Knockout biology Cell adhesion molecule NF-kappa B Chemokines CX3C Cell biology Chemotaxis Leukocyte P-Selectin medicine.anatomical_structure Cytokines I-kappa B Proteins medicine.symptom Rheology Cardiology and Cardiovascular Medicine Endothelium Recombinant Fusion Proteins T cell Hypercholesterolemia Myocytes Smooth Muscle Inflammation Proinflammatory cytokine Apolipoproteins E Cell Adhesion medicine Animals Chemokine CX3CL1 Monocyte Membrane Proteins Rats IκBα Gene Expression Regulation Immunology biology.protein Endothelium Vascular |
| Zdroj: | Circulation Research. 94:776-784 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/01.res.0000121105.72718.5c |
| Popis: | Leukocyte recruitment is crucial for the response to vascular injury in spontaneous and accelerated atherosclerosis. Whereas the mechanisms of leukocyte adhesion to endothelium or matrix-bound platelets have been characterized, less is known about the proadhesive role of smooth muscle cells (SMCs) exposed after endothelial denudation. In laminar flow assays, neointimal rat SMCs (niSMCs) supported a 2.5-fold higher arrest of monocytes and "memory" T lymphocytes than medial SMCs, which was dependent on both P-selectin and VLA-4, as demonstrated by blocking antibodies. The increase in monocyte arrest on niSMCs was triggered by the CXC chemokine GRO-alpha and fractalkine, whereas "memory" T cell arrest was mediated by stromal cell-derived factor (SDF)-1alpha. This functional phenotype was paralleled by a constitutively increased mRNA and surface expression of P-selectin and of relevant chemokines in niSMCs, as assessed by real-time PCR and flow cytometry. The increased expression of P-selectin in niSMCs versus medial SMCs was associated with enhanced NF-kappaB activity, as revealed by immunofluorescence staining for nuclear p65 in vitro. Inhibition of NF-kappaB by adenoviral IkappaBalpha in niSMCs resulted in a marked reduction of increased leukocyte arrest in flow. Furthermore, P-selectin expression by niSMCs in vivo was confirmed in a hypercholesterolemic mouse model of vascular injury by double immunofluorescence and by RT-PCR after laser microdissection. In conclusion, we have identified a NF-kappaB-mediated proinflammatory phenotype of niSMCs that is characterized by increased P-selectin and chemokine expression and thereby effectively supports leukocyte recruitment. |
| Databáze: | OpenAIRE |
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