Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease

Malizia, Giuseppe; Calabrese, A.; Cottone, Mario; Raimondo, Massimo; Trejdosiewicz, Ludwik K.; Smart, C J; Oliva, L; Pagliaro, Luigi

doi:10.1016/0016-5085(91)90595-c

Cited by 194 publications

(92 citation statements)

References 40 publications

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“…Recent studies in this laboratory and elsewhere have demonstrated the expression of the adhesion molecules E-selectin and ICAM1 at sites of active inflammation in patients with IBD (24,25). As expected these adhesion molecules are present in both UC and CD.…”

Section: Introductionsupporting

confidence: 67%

Attenuation of colitis in the cotton-top tamarin by anti-alpha 4 integrin monoclonal antibody.

Podolsky¹,

Lobb²,

King³

et al. 1993

J. Clin. Invest.

320

147

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Recent studies have demonstrated the induced expression of endothelial adhesion molecules including E-selectin (also called endothelial leukocyte adhesion molecule-i), vascular cell adhesion molecule and intercellular adhesion molecule in actively involved mucosa of patients with ulcerative colitis and Crohn's disease. Similar induction has been demonstrated in the colon of the Cotton-top tamarin (CTU), a New World primate that experiences a spontaneous acute and chronic colitis resembling ulcerative colitis.To assess the potential importance of leukocyte adhesion as a necessary step in acute colitis, the effect of parenteral mAb directed against adhesion molecules on CIT colitis was evaluated in placebo-controlled blinded trials. Serial administration ofeither of two anti-E-selectin mAb designated BB1 1 and EH8 effectively coated endothelial surfaces expressing this vascular adhesion molecule. Although colitis activity was slightly diminished after the 10-d treatment period in CIT receiving either BB1 1 or EH8, this reduction was not significantly different than that seen in animals given a placebo control when assessed by a previously validated standardized scale of inflammatory activity: mean histologic activity grade 2.2±0.2 pretreatment vs 1.5±0.5 posttreatment in group receiving mAb and 2.1±0.1 pretreatment vs 1.3±0.5 posttreatment in the placebo group (P > 0.2). In contrast, administration of an anti-a4 integrin mAb designated HP1 /2 that binds VLA4 (a4f31) and presumably a4187 integrins resulted in significant attenuation of acute colitis when compared to both pretreatment activity index (P = 0.005) and the placebo control group (P < 0.01 ): mean histologic activity grade 1.6±0.3 pretreatment vs 0.2±0.1 posttreatment in the group receiving HP1 /2 and 1.8±0.5 pretreatment and 1.2±0.2 posttreatment in the placebo control group.These studies using a model of spontaneous colitis in the CMT demonstrate the feasibility of modulation of leukocytevascular adhesion and/or other integrin-mediated events possibly including T cell aggregation and T cell-stromal interactions, as well as lymphocyte homing. These results suggest both that these processes are important and possibly essential elements in sustaining acute colitis and that their disruption may result in therapeutic benefit. (J. Clin. Invest. 1993. 92: Address correspondence to Daniel K. Podolsky, M.D., GI Unit, Jackson 7,

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Section: Introductionsupporting

confidence: 67%

Attenuation of colitis in the cotton-top tamarin by anti-alpha 4 integrin monoclonal antibody.

Podolsky¹,

Lobb²,

King³

et al. 1993

J. Clin. Invest.

320

147

View full text Add to dashboard Cite

show abstract

“…Because we and others have previously demonstrated that cutaneous DHR is characterized by the dual, asynchronous, de novo expression of E-selectin and VCAM-1 (8-10, 12, 43) (31,32,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54) and that these endothelial adhesion proteins are expressed at inflammatory sites (1)(2)(3)(4)(5)(6)(7)(9)(10)(11)(12). Although it has been hypothesized from these data that endothelial and leukocyte adhesion molecules play a fundamental role in leukocyte recruitment and subsequent tissue injury at an inflammatory site, only recently, using neutralizing mAbs and animal models of inflammatory disease, has this role been documented.…”

Section: Discussionmentioning

confidence: 99%

“…Adhesion proteins on endothelium, such as P-selectin, E-selectin, vascular cell adhesion molecule 1 (VCAM-1),' or intercellular adhesion molecule 1 (ICAM-1) are either expressed de novo (VCAM-1, E-selectin), redistributed to the cell membrane from cytoplasmic stores (P-selectin), or upregulated from basal levels (ICAM-1) in multiple organs with various kinds of inflammatory disease activity, including inflammatory bowel disease ( 1,2), sepsis (3), AIDS encephalitis in monkeys (4), complement-mediated pulmonary injury in rats (5), allograft rejection (6,7), and cutaneous delayed hypersensitivity (DHR) (8)(9)(10)(11)(12). In experimental models of inflammatory disease, there are close spatial and temporal associations between the expression of endothelial adhesion molecules and the subsequent localization of leukocytes at the inflammatory site (9)(10)(11)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Recruitment of lymphocytes during cutaneous delayed hypersensitivity in nonhuman primates is dependent on E-selectin and vascular cell adhesion molecule 1.

Silber

Newman²,

Sasseville³

et al. 1994

J. Clin. Invest.

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Previous investigations of cutaneous delayed hypersensitivity (DHR) in humans and animals have demonstrated that lymphocyte recruitment from blood is temporally and spatially associated with the de novo, asynchronous expression of both vascular cell adhesion molecule 1 (VCAM-1 ) and E-selectin on dermal endothelium. In this study, DHR was induced in rhesus monkeys sensitized against tuberculin in order to investigate the contribution of E-selectin and VCAM-1 in lymphocyte recruitment to skin. Intravenous infusions of neutralizing doses of F(ab')2 fragments of murine antibodies to either E-selectin or VCAM-1 during the early inductive phases of DHR showed that murine IgG localized to dermal endothelium at the site of DHR in a pattern kinetically similar to the expression of each endothelial adhesion protein. Most importantly, the relative numbers of lymphocytes localized to the inflammatory site were significantly reduced in DHR modified with infusions of antibodies to either VCAM-1 or E-selectin, while the numbers of lymphocytes recruited to skin in the animal given F(ab')2 fragments of an irrelevant murine monoclonal antibody of the same isotype and at the same dose were not changed. Moreover, in individual animals, the relative inhibition achieved with a particular antibody was proportional to the magnitude of expression of the targeted adhesion protein. Therefore, both VCAM-1 and E-selectin are functionally relevant in the genesis of cutaneous DHR, and each appears to contribute to lymphocyte recruitment in relation to its relative degree of expression in any one particular animal. (J. Clin. Invest. 1994Invest. . 93:1554Invest. -1563

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“…For example, an increased immunoreactivity for E-selectin and ICAM-1 expression has also been shown in colonic biopsy specimens from patients with inflammatory bowel disease [16,17]. E-selectin is the other endothelial selectin that can support leukocyte recruitment in inflamed post-capillary venules.…”

Section: Introductionmentioning

confidence: 99%

Intestinal inflammation in adhesion molecule-deficient mice: an assessment of P-selectin alone and in combination with ICAM-1 or E-selectin

McCafferty

Smith

Granger

et al. 1999

Journal of Leukocyte Biology

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Biopsy specimens from patients with inflammatory bowel disease have demonstrated an up-regulation of P-selectin, suggesting a role for P-selectin in intestinal inflammation. We examined the role of P-selectin in experimental intestinal inflammation using mice deficient in P-selectin alone or in combination with either ICAM-1 or E-selectin. Colitis was induced using acetic acid or trinitrobenzene sulfonic acid (TNBS). Damage scores and neutrophil infiltration 24 h post acetic acid were not different between wild-type and P-selectin-or P-selectin/ICAM-1-deficient mice, whereas P/E-selectin-deficient mice had enhanced leukocyte recruitment and damage. At 72 h an attenuation in damage scores and a slight decrease in neutrophil infiltration was observed in the P-and P/ICAM-deficient animals. The P/E-selectin-deficient mice maintained enhanced leukocyte recruitment and damage. In wild-type mice P-selectin expression was elevated 48 and 72 h post acetic acid-induced inflammation. Surprisingly, P-selectin or P-selectin/ICAM-1 deficiency did not improve the inflammation induced by TNBS over 7 days. In fact, increased mortality was observed. Antiadhesion therapy may play only a limited, beneficial role and often a detrimental role in intestinal inflammation. J. Leukoc. Biol. 66: 67-74; 1999.

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Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease

Cited by 194 publications

References 40 publications

Attenuation of colitis in the cotton-top tamarin by anti-alpha 4 integrin monoclonal antibody.

Attenuation of colitis in the cotton-top tamarin by anti-alpha 4 integrin monoclonal antibody.

Recruitment of lymphocytes during cutaneous delayed hypersensitivity in nonhuman primates is dependent on E-selectin and vascular cell adhesion molecule 1.

Intestinal inflammation in adhesion molecule-deficient mice: an assessment of P-selectin alone and in combination with ICAM-1 or E-selectin

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