Increased expression of CD146, a new marker of the endothelial junction in active inflammatory bowel disease

Bardin, Nathalie; Reumaux, Dominique; Geboes, K.; Colombel, J.F.; Blot‐Chabaud, Marcel; Sampol, José; Duthilleul, Patrick; Dignat-George, Françoise

doi:10.1097/01.mib.0000194181.46930.88

Cited by 68 publications

(66 citation statements)

References 25 publications

(25 reference statements)

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“…In addition, endothelial MCAM is very likely involved in this process. First, similar to VCAM-1, MCAM isoforms are up-regulated in inflammatory diseases (68) and following our data act as rolling receptors. Second, restriction of endothelial MCAM-l luminal expression to activated endothelium and specific arrest of MCAM-l ϩ activated lymphocytes on the MCAM-l-expressing cell monolayer suggest an additional role for the endothelial MCAM-l isoform in the targeting to inflammation sites.…”

Section: Mcam-l Is Expressed In All Cd146mentioning

confidence: 99%

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Dual Role of Melanoma Cell Adhesion Molecule (MCAM)/CD146 in Lymphocyte Endothelium Interaction: MCAM/CD146 Promotes Rolling via Microvilli Induction in Lymphocyte and Is an Endothelial Adhesion Receptor

Guezguez

Vigneron

Lamerant

et al. 2007

The Journal of Immunology

103

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The melanoma cell adhesion molecule (MCAM)/CD146 is expressed as two isoforms differing by their cytoplasmic domain (MCAM long (MCAM-l) and MCAM short (MCAM-s)). MCAM being expressed by endothelial cells and activated T cells, we analyzed its involvement in lymphocyte trafficking. The NK cell line NKL1 was transfected by MCAM isoforms and submitted to adhesion on both the endothelial cell monolayer and recombinant molecules under shear stress. MCAM-l transfection reduced rolling velocity and increased NKL1 adhesion on the endothelial cell monolayer and VCAM-1. Scanning electron microscopy revealed that MCAM-l induced microvilli formation and extension. In contrast, MCAM short or mock transfection had no effect on adhesion of NKL1 cells and microvilli formation. As shown by mutagenesis, serine 32 of the MCAM-l cytoplasmic tail, belonging to a putative protein kinase C phosphorylation site, was necessary for MCAM-l-actin cytoskeleton interaction and microvilli induction. Accordingly, chelerythrine chloride, a protein kinase C inhibitor, abolished MCAM-l-induced microvilli and rolling of MCAM-l-transfected NKL1 cells. Inhibition of adhesion under shear stress by anti-MCAM Abs suggested that both lymphoid MCAM-l and endothelial MCAM were also directly involved in lymphocyte endothelium interaction. MCAM-l-transfected NKL1 and activated CD4 T cells adhered to rMCAM under shear stress whereas anti-MCAM Ab treatment inhibited this process. Taken together, these data establish that MCAM is involved in the initial steps of lymphocyte endothelium interaction. By promoting the rolling on the inflammation marker VCAM-1 via microvilli induction and displaying adhesion receptor activity involving possible homophilic MCAM-l-MCAM-l interactions, MCAM might be involved in the recruitment of activated T cells to inflammation sites.

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Section: Mcam-l Is Expressed In All Cd146mentioning

confidence: 99%

“…Reciprocally, regulation of MCAM expression in inflamed endothelium is correlated with the potential role of endothelial MCAM in the targeting of activated T cell to inflammation sites. Recently, increased expression of CD146 was detected in endothelial cells in active inflammatory bowel disease (68).…”

Section: Mcam-l Is Expressed In All Cd146mentioning

confidence: 99%

Dual Role of Melanoma Cell Adhesion Molecule (MCAM)/CD146 in Lymphocyte Endothelium Interaction: MCAM/CD146 Promotes Rolling via Microvilli Induction in Lymphocyte and Is an Endothelial Adhesion Receptor

Guezguez

Vigneron

Lamerant

et al. 2007

The Journal of Immunology

103

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“…Along these lines is also the observation that CD146, a novel marker of endothelial junction remodeling, is highly expressed on ECs in intestinal biopsies from both CD and UC, with a decrease in the soluble form of CD146 in relation to active disease. 98 In addition, increased serum and/or tissue levels of several proangiogenic factors have been reported in patients with active IBD. 99 -102 The notion that immune-nonimmune interactions are important for the maintenance and propagation of inflammation-induced mucosal angiogenesis is substantiated by recent studies that identify the critical role of the CD40-CD40L pathway in immunedriven angiogenesis.…”

Section: Angiogenesis In Ibdmentioning

confidence: 99%

Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades

Deban

Correale

Vetrano

et al. 2008

The American Journal of Pathology

124

100

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The etiology of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), is still largely unknown. However, it is now clear that the abnormalities underlying pathogenesis of intestinal inflammation are not restricted to those mediated by classic immune cells but also involve nonimmune cells. In particular, advances in vascular biology have outlined a central and multifaceted pathogenic role for the microcirculation in the initiation and perpetuation of IBD. The microcirculation and its endothelial lining play a crucial role in mucosal immune homeostasis through tight regulation of the nature and magnitude of leukocyte migration from the intravascular to the interstitial space. Chronically inflamed IBD microvessels display significant alterations in microvascular physiology and function compared with vessels from healthy and uninvolved IBD intestine. The investigation into human IBD has demonstrated how endothelial activation present in chronically inflamed IBD microvessels results in a functional phenotype that also includes leakiness, chemokine and cytokine expression, procoagulant activity, and angiogenesis. This review contemplates the newly uncovered contribution of intestinal microcirculation to pathogenesis and maintenance of chronic intestinal inflammation. In particular, we assess the multiple roles of the microvascular endothelium in innate immunity, leukocyte recruitment, coagulation and perfusion, and immune-driven angiogenesis in IBD.

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“…This adhesion molecule is involved in later stages of metastasis and has been identified as an indicator of angiogenesis, but its specific biological role in angiogenesis is not well understood (53,137). CD146 is reported to be upregulated in endothelial cells of CD and UC patients (12). High expression of these molecules in IBD may lead to increases in angiogenic factorproducing cell types, contributing to pathological angiogenesis during disease.…”

Section: Angiogenic Mediators In Ibd and Experimental Colitismentioning

confidence: 99%

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Chidlow

Shukla²,

Grisham³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

144

114

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Chidlow JH Jr, Shukla D, Grisham MB, Kevil CG. Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues. Am J Physiol Gastrointest Liver Physiol 293: G5-G18, 2007. First published April 26, 2007; doi:10.1152/ajpgi.00107.2007.-Angiogenesis is now understood to play a major role in the pathology of chronic inflammatory diseases and is indicated to exacerbate disease pathology. Recent evidence shows that angiogenesis is crucial during inflammatory bowel disease (IBD) and in experimental models of colitis. Examination of the relationship between angiogenesis and inflammation in experimental colitis shows that initiating factors for these responses simultaneously increase as disease progresses and correlate in magnitude. Recent studies show that inhibition of the inflammatory response attenuates angiogenesis to a similar degree and, importantly, that inhibition of angiogenesis does the same to inflammation. Recent data provide evidence that differential regulation of the angiogenic mediators involved in IBD-associated chronic inflammation is the root of this pathological angiogenesis. Many factors are involved in this phenomenon, including growth factors/cytokines, chemokines, adhesion molecules, integrins, matrix-associated molecules, and signaling targets. These factors are produced by various vascular, inflammatory, and immune cell types that are involved in IBD pathology. Moreover, recent studies provide evidence that antiangiogenic therapy is a novel and effective approach for IBD treatment. Here we review the role of pathological angiogenesis during IBD and experimental colitis and discuss the therapeutic avenues this recent knowledge has revealed. inflammation; T cells; growth factors; adhesion molecules; antiangiogenesis ANGIOGENESIS PLAYS AN IMPORTANT role in many chronic inflammatory diseases including but not limited to diabetic retinopathy, atherosclerosis, rheumatoid arthritis, hypercholesterolemia, and psoriasis. It has been suggested that the angiogenic components of these diseases contribute to and exacerbate disease conditions (26, 31). Recent findings, both clinical and experimental, indicate that angiogenesis also plays a crucial role in the inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC) (31,37,58,131,155). Development of new vasculature during chronic inflammation may play a negative "pathological" role by contributing to increased inflammatory responses due to dysfunctional new vessel architecture and increases in the recruitment of inflammatory cell types. Importantly, recent data have shown that angiogenic inhibition during chronic inflammatory diseases attenuates further inflammation and disease pathology (31, 37, 51). As such, expanding our knowledge of how pathological angiogenesis occurs during IBD will further our ability to treat patients with these diseases. IBD PathogenesisCD and UC are idiopathic inflammatory disorders of the intestine and/or colon in which patients suffer from rectal bleeding, severe...

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Increased expression of CD146, a new marker of the endothelial junction in active inflammatory bowel disease

Cited by 68 publications

References 25 publications

Dual Role of Melanoma Cell Adhesion Molecule (MCAM)/CD146 in Lymphocyte Endothelium Interaction: MCAM/CD146 Promotes Rolling via Microvilli Induction in Lymphocyte and Is an Endothelial Adhesion Receptor

Dual Role of Melanoma Cell Adhesion Molecule (MCAM)/CD146 in Lymphocyte Endothelium Interaction: MCAM/CD146 Promotes Rolling via Microvilli Induction in Lymphocyte and Is an Endothelial Adhesion Receptor

Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

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