Stimulatory Interactions between Human Coronary Smooth Muscle Cells and Dendritic Cells (original) (raw)
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Journal of Clinical Investigation, 1993
Endothelial attachment is the initial step in leukocyte recruitment into developing atherosclerotic lesions. To determine whether vascular cell adhesion molecule-i (VCAM-1) expression may play a role in inflammatory cell recruitment into human atherosclerotic lesions, immunohistochemistry was performed with a polyclonal rabbit antisera, raised against recombinant human VCAM-1, on 24 atherosclerotic coronary plaques and 11 control coronary segments with nonatherosclerotic diffuse intimal thickening from 10 patients. Immunophenotyping was performed on adjacent sections to identify smooth muscle cells, macrophages, and endothelial cells. To confirm VCAM-1-expressing cell types, double immunostaining with VCAM-1 antisera and each of the cell-specific markers and in situ hybridization were performed.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2000
Vascular cell adhesion molecule (VCAM)-1 is induced in smooth muscle cells after arterial injury, in which it has been implicated in the recruitment of inflammatory cells to the site of injury. To investigate the effect of hypercholesterolemia on VCAM-1 induction after injury and the role of VCAM-1 in neointimal response to injury, we injured the carotid artery of wild-type and apolipoprotein E null (KO) mice fed normal and high cholesterol chow. We demonstrate a graded response of VCAM-1 induction as well as monocyte/macrophage infiltration by immunohistochemistry 3 days after injury that correlated with increasing circulating cholesterol levels. Three weeks after injury, KO mice fed high cholesterol chow (KO HC group) had a significantly greater neointimal formation compared with wild-type and KO mice fed normal chow (PϽ0.05). Inhibition of VCAM-1 function in the KO HC group by monoclonal antibody treatment significantly reduced monocyte/macrophage infiltration and neointimal formation. There was reduced ␣-actin expression in KO HC mice 7 days after injury that was partially inhibited by VCAM-1 antibody treatment. Cell migration in an in vitro injury model was partially inhibited by monoclonal VCAM-1 antibody treatment. We propose an additional role for VCAM-1 in smooth muscle cell activation and neointimal formation after injury.
Dendritic cells in neointima formation after rat carotid balloon injury
Journal of the American College of Cardiology, 2003
We sought to evaluate: 1) the contribution of dendritic cells (DCs); and 2) the impact of B-cell lymphoma 2 protein (Bcl-2), a central anti-apoptotic protooncogene, and of heat shock protein 47 (HSP47), indicating subsequent collagen deposition, in neointima formation after angioplasty. BACKGROUND The origin of neointimal cells and the factors that promote their accumulation are still unclear. Previous studies reported intimal presence of DCs and suggested cells of primarily extravascular origin to contribute to arterial repair.
Endothelial adhesion molecule expression in an in vitro model of inflammation
Clinica Chimica Acta, 2002
Background: Cytokines influence the expression of adhesion molecules and hence, regulate the passage of leucocytes from the blood to the site of inflammation causing leucocyte accumulation and the modulation of the nature and progression of inflammatory responses. They form a complex communication network causing results which are not determined by the effects of a single cytokine but especially by the interaction of several cytokines. Method: For the determination of adhesion molecule expression on the surface of enzymatically detached endothelial cells, flow cytometry is applied. Fluorescence-conjugated mouse monoclonal antibodies directed against VCAM-1, ICAM-1, PECAM-1, CD34, E-and P-selectin are used. Results: We clearly demonstrate that ICAM-1, PECAM-1, P-selectin and CD34 are-in relation to an incubation cocktail containing solely TNF-a, IL-1h and IFN-g-altered antagonistically by the supplementary addition of the inflammatory cytokines IL-2 and IL-6 as well as the anti-inflammatory cytokines IL-4 and IL-10, whereas VCAM-1 is synergistically enhanced under the same test conditions. Conclusion: The results of our in vitro investigations show that the effects of a single cytokine within a multicomponent cytokine combination on endothelial adhesion molecule expression are strongly influenced by the nature of the other cytokines present in the combination tested.
Circulation Research, 1994
Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin are inducible proteins involved in cell-cell adhesion. Immunohistochemical studies have indicated that human atherosclerotic plaques contain smooth muscle cells (SMCs) that express ICAM-1 and VCAM-1. Recently, we demonstrated that SMCs in culture express a functionally active cytokine-inducible ICAM-1. SMCs and mononuclear cells participate in the local accumulation of cytokines and related growth factors in atherosclerotic lesions. Therefore, we determined the effects of different cytokines and growth factors on mRNA content and cell surface expression of VCAM-1, ICAM-1, and E-selectin in cultured human aortic SMCs by Northern blotting, quantitative polymerase chain reaction amplification, and immunofluorescence flow cytometry. Under basal conditions of cultivation, both VCAM-1 mRNA and membrane expression of VCAM-1 were low and were induced very little by interleukin-1,3 (100 U/mL). Plateletderived growth factor or transforming growth factor-,8 decreased VCAM-1 mRNA basal expression. Treatment of SMCs with tumor necrosis factor-a (TNF-a) led to an increase in both ulascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are members of the immunoglobulin gene superfamily. VCAM-1 is a ligand for very late antigen-4, a f3i integrin expressed on monocytes and lymphocytes but not neutrophils; ICAM-1 is a ligand for lymphocyte function-associated antigen-1, a 82 integrin expressed on all leukocytes. Along with endothelial leukocyte adhesion molecule-1, now designed E-selectin, these molecules are inducible proteins involved in cell-cell adhesion (reviewed in References 1 and 2). VCAM-1 is present in activated endothelial cells (ECs), macrophages, lymphoid dentritic cells, and stromal fibroblasts in the bone marrow. Expression of this molecule is upregulated by tumor necrosis factor-a (TNF-a), interleukin-1 (IL)-1, IL-4, and perhaps other cytokines. ICAM-1 is constitutively expressed at low levels on the surface of hematopoietic cells and certain nonhematopoietic cells, including fibroblasts, vascular ECs, and epithelial cells. It is strongly upregulated by cyto-VCAM-1 mRNA and cell surface expression for VCAM-1 in a dose-and time-dependent manner. Interferon-y induced a weak increase in VCAM-1 mRNA expression, with no synergistic effect on the stimulation by TNF-a. Various differences were noted between the expression of ICAM-1 and VCAM-1 genes, because interleukin-i,3 induced substantial amounts of ICAM-1 but not VCAM-1. The addition of interferon-y delays the time at which peak expression of ICAM-1 in response to TNF-a stimulation occurs. Under our conditions, we did not detect any expression of E-selectin by SMCs. These results suggest that cytokines regulate VCAM-1 and ICAM-1 expression on arterial SMCs and could play an important role in the pathophysiology of inflammatory and immune processes in atherosclerosis. (Circ Res. 1994;74:225-234.) Key Words * tumor necrosis factor-a * interleukin-1,3 d interferon-y * platelet-derived growth factor * transforming growth factor-P * smooth muscle cells * vascular cell adhesion molecule-1 * intercellular adhesion molecule-1atherosclerosis
Adhesion molecule expression in symptomatic and asymptomatic carotid stenosis
Neurology, 2003
Background: Prior studies have suggested a central role for cellular adhesion molecules (CAMs) in the pathophysiology and symptoms of atherosclerotic carotid plaques (CPs). Objective: This study examined the role of CAMs in symptom generation in patients with advanced carotid artery disease. Methods: Ninety-two consecutive patients underwent carotid endarterectomy, six for both sides (54 symptomatic and 41 asymptomatic CPs). Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and E-selectin were immunostained in fresh-frozen CP specimens and examined semiquantitatively in the endothelium and intima-media. Plasma concentrations of soluble ICAM-1 and sVCAM-1 were analyzed by ELISA. Results: Endothelial expression of ICAM-1, VCAM-1, P-selectin, and E-selectin did not differ between symptomatic and asymptomatic CPs, but endothelial ICAM-1 was associated with serum sensitized C-reactive protein levels (p ϭ 0.026). However, there was less ICAM-1 expression in the intima-media of the symptomatic CPs (p ϭ 0.022), and there was a similar, but nonsignificant tendency for VCAM-1. Soluble ICAM-1 and soluble VCAM-1 were not associated with the symptom status. Conclusions: In contrast to earlier studies, it was found that symptomatic carotid disease is not associated with increased expression of adhesion molecules in the endothelium of advanced carotid plaques or in circulation. Rather, there was less expression of adhesion molecules in the intima-media of symptomatic carotid plaques.