Amelioration of chronic murine experimental colitis by inhibition of mucosal addressin cell adhesion molecule-1 (MAdCAM-1)

Kato, Shingo; Hokari, Ryota; Matsuzaki, Koji; Iwai, Atsuhiro; Kawaguchi, Atsushı; Nagao, Shigeaki; Miyahara, Tohru; Itoh, Kazuro; Miura, Soichiro

doi:10.1016/s0016-5085(00)84435-2

Cited by 79 publications

(111 citation statements)

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“…Similar results were obtained after blocking MadCAM-1, the ligand for the intestinal homing receptor, a4b7 integrin [15,16]. Crohn's disease patients subjected to short-term treatment with Natalizumab, a recombinant monoclonal antibody against a4 integrin, entered remission more frequently than placebo patients, although the drug had only a partial anti-inflammatory effect.…”

Section: Introductionsupporting

confidence: 68%

“…However, when using a4 blocking antibodies both VCAM-1/a4b1 as well as MAdCAM-1/a4b7 integrin interactions can be blocked. Previous studies, both in patients and in various animal models, have shown that short-term blockade of a4 integrin [11][12][13][14], b7 integrin [15] or MAdCAM-1 [15,16] ameliorates intestinal inflammation. Crohn's disease patients who received one to two injections of Natalizumab, a recombinant humanized mAb to a4 integrins, entered remission more frequently than placebo-treated patients [11,12].…”

Section: Discussionmentioning

confidence: 99%

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Long-term treatment with anti-α4 integrin antibodies aggravates colitis in Gαi2-deficient mice

et al. 2005

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Targeted deletion of the heterotrimeric G protein, Gai2, in mice induces lethal colitis closely resembling ulcerative colitis. In chronic colitis, migration of circulating leukocytes into the intestinal mucosa is partially dependent on a4 integrins. In previous studies, short-term administration of anti-a4 integrin antibodies has been shown to attenuate intestinal inflammation, and here we elucidate the effect of long-term administration of anti-a4 integrin antibodies on colitis in Gai2 -/-mice. Long-term blockade of a4 integrin significantly increased the severity of colitis in Gai2 -/-mice. The inflammation was confined to the colon, associated with increased cancer in situ, destruction of crypt architecture, and increased production of IL-1b, TNF-a and IFN-c. Blockade of a4 integrin reduced the recruitment of activated T cells to the small intestine. In strong contrast, there were significantly higher numbers of activated T cells in the colonic lamina propria and epithelium, most probably due to in situ proliferation. Furthermore, treatment with a4 integrin antibodies induced decreased levels of total IgA and IgG in sera, whereas total IgM levels were unchanged. These new findings may have implications in the understanding of the progression of chronic intestinal inflammation.See accompanying commentary: http://dx

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Section: Introductionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Long-term treatment with anti-α4 integrin antibodies aggravates colitis in Gαi2-deficient mice

et al. 2005

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“…Evidence in support comes from studies of experimental murine colitis models in which VCAM-1 mediated adhesion blockade significantly ameliorated inflammation whereas MAdCAM-1 blockade was much less effective. 12 Small bowel and colonic homing lymphocytes also express chemokine receptors that do not generally dictate tissue-specific homing but rather define an activated pro-inflammatory phenotype. CXCR3, CCR5 and CXCR4 are detectable on gut-homing lymphocytes, with their expression dramatically enhanced during states of inflammation.…”

Section: Lymphocyte Homing To the Gutmentioning

confidence: 99%

Lymphocyte homing in the pathogenesis of extra-intestinal manifestations of inflammatory bowel disease

et al. 2004

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-Inflammatory bowel disease is associated with extra-intestinal manifestations which occur either at the same time as flares of bowel inflammation (skin and eye disease) or run a course that is independent to inflammation in the bowel (liver and some joint syndromes). It has been suggested that the skin and eye complications occur as a consequence of the recruitment of activated effector cells released from the gut into the circulation to extra-intestinal site where they cause acute damage. However, this does not explain how patients can develop primary sclerosing cholangitis many years after having their colon removed for colitis. We propose that longlived populations of memory lymphocytes arise as a consequence of bowel inflammation and that these cells express homing receptors that direct their subsequent migration not only to the gut but also to the liver. These long-lived cells may recirculate to the liver for many years and, in the absence of a local activating stimulus, will not cause damage. However, if they are subsequently activated in the liver this will lead to the development of inflammation and tissue damage which promotes the recruitment of more mucosal lymphocytes resulting in persistent inflammation and disease. The recent findings that MAdCAM-1 and CCL25, previously thought to be restricted to the gut, are up-regulated in the liver during inflammatory liver diseases that complicate IBD support the concept that common mechanisms control lymphocyte recruitment to the inflamed liver and gut.

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“…This interaction appears to be important for T cell homing to the lamina propria as intestinal T cell numbers are reduced in ␤ 7 integrindeficient mice (5). In addition, mAbs that recognize ␣ 4 ␤ 7 or MAd-CAM-1 inhibit lymphocyte migration into Peyer's patches and the lamina propria (13), and inhibit the generation of intestinal inflammation in murine models (14,15).…”

mentioning

confidence: 99%

Integrin αE(CD103)β7 Mediates Adhesion to Intestinal Microvascular Endothelial Cell Lines Via an E-Cadherin-Independent Interaction

Strauch

Mueller

et al. 2001

The Journal of Immunology

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Integrins are important for T cell interactions with endothelial cells. Because the integrin αEβ7 is expressed on some circulating gut-homing T cells and as T cell numbers are reduced in the intestinal lamina propria of αE-deficient mice, we evaluated whether αEβ7 mediates binding to intestinal endothelial cells. We found that anti-αEβ7 mAbs partially blocked the binding of cultured intraepithelial T cells to human intestinal microvascular endothelial cells (HIMEC). Furthermore, αEβ7-transfected K562 cells bound more efficiently than vector-transfected K562 cells to HIMEC. Finally, HIMEC bound directly to an αEβ7-Fc fusion protein. These interactions were partially blocked by anti-αEβ7 mAbs, and endothelial cell binding to the αEβ7-Fc was dependent upon the metal ion-dependent adhesion site within the αE A domain. Of note, the HIMEC lacked expression of E-cadherin, the only known αEβ7 counterreceptor as assessed by functional studies, flow cytometry, and RT-PCR. Thus, HIMEC/αEβ7 binding was independent of E-cadherin. In addition, this interaction appeared to be tissue selective, as HIMEC bound to the αEβ7-Fc, whereas microvascular endothelial cells from the skin did not. Finally, there was evidence for an αEβ7 ligand on intestinal endothelial cells in vivo, as αEβ7 expression enhanced lymphocyte binding around vessels in the lamina propria in tissue sections. Thus, we have defined a novel interaction for αEβ7 at a nonepithelial location. These studies suggest a role for αEβ7 in interactions with the intestinal endothelium that may have implications for intestinal T cell homing or functional responses.

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Amelioration of chronic murine experimental colitis by inhibition of mucosal addressin cell adhesion molecule-1 (MAdCAM-1)

Cited by 79 publications

References 0 publications

Long-term treatment with anti-α4 integrin antibodies aggravates colitis in Gαi2-deficient mice

Long-term treatment with anti-α4 integrin antibodies aggravates colitis in Gαi2-deficient mice

Lymphocyte homing in the pathogenesis of extra-intestinal manifestations of inflammatory bowel disease

Integrin αE(CD103)β7 Mediates Adhesion to Intestinal Microvascular Endothelial Cell Lines Via an E-Cadherin-Independent Interaction

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