ICAM‐2 Provides a Costimulatory Signal for T Cell Stimulation by Allogeneic Class II MHC

Carpenito, Carmine; Pyszniak, Andrew M.; Takei, Fumio

doi:10.1046/j.1365-3083.1997.d01-391.x

Cited by 13 publications

(9 citation statements)

References 26 publications

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“…This is supported by observations in experimental arthritis, where administration of anti-CD44 antibodies reduces arthritic activity. [27][28][29] In addition, CD102 (intercellular adhesion molecule-2 (ICAM-2)), an adhesion molecule that has an important role in transmigration and costimulatory signalling, 30 was down regulated on EC. In accordance with the data presented, LEF-M also appears to affect cell adhesion.…”

Section: Discussionmentioning

confidence: 99%

Leflunomide inhibits transendothelial migration of peripheral blood mononuclear cells

Grisar

Aringer²,

Köller³

et al. 2004

Annals of the Rheumatic Diseases

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Objectives: To test whether the active metabolite of leflunomide (LEF-M), in addition to blocking the proliferation of activated lymphocytes by inhibiting dihydro-orotate dehydrogenase (DHODH), influences the transendothelial migration (TEM) of peripheral blood mononuclear cells (PBMC). Methods:In an in vitro model of PBMC transmigration through an endothelial cell (EC) barrier, PBMC were re-collected in three groups: cells not adherent to the EC, cells bound to, and cells which had migrated through, the EC layer. Experiments in which cells were pretreated with LEF-M (in the absence or in the presence of uridine) were compared with parallel experiments in the presence of medium alone. Results: Preincubation of EC with LEF-M led to a 36 (SEM 16)% reduction in PBMC TEM (p,0.05). Likewise, preincubation of PBMC induced a reduction in their TEM of 39 (9)% (p,0.005). Incubation of both PBMC and EC with LEF-M had an additive effect (mean reduction of 48 (6)%, p,0.005). Incubation of PBMC with LEF-M also decreased monocytic CD44 expression (p,0.005) and PBMC-hyaluronan binding (p,0.05). Incubation of cells with LEF-M and uridine in addition to LEF-M reversed the inhibition of migration, suggesting that the observed effects were due to DHODH inhibition. Fluorocytometric analysis of PBMC subsets within the migrated population showed a decrease of monocytes, but not of B or T cells, after LEF-M treatment. Conclusions: LEF-M reduces monocytic adhesion molecule expression and TEM and may thus interfere with monocyte and EC activities in RA. Thus, the clinical effects of leflunomide may, at least in part, be due to blocking cell traffic into the inflamed synovia.

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Section: Discussionmentioning

confidence: 99%

Leflunomide inhibits transendothelial migration of peripheral blood mononuclear cells

Grisar

Aringer²,

Köller³

et al. 2004

Annals of the Rheumatic Diseases

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“…Human ICAM-2 is a counter receptor for lymphocyte function-associated antigen-1 (21) and may provide a costimulatory signal for T cell stimulation by allogeneic class II major histocompatibility complex (22). In human tissues, the expression of ICAM-2 is restricted largely to endothelial cells and megakaryocytes (23).…”

Section: From the Immunology Research Center St Vincent's Hospital mentioning

confidence: 99%

The Human ICAM-2 Promoter is Endothelial Cell-specific in Vitro and in Vivo and Contains Critical Sp1 and GATA Binding Sites

Cowan

Tsang

Pedic

et al. 1998

Journal of Biological Chemistry

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The expression of intercellular adhesion molecule 2 (ICAM-2) in adult tissues is restricted to vascular endothelial cells and megakaryocytes. We have previously shown that the endothelial-specific in vivo activity of the human ICAM-2 promoter is contained within a small (0.33-kilobase (kbp)) 5-flanking region of the gene. Here we describe the in vitro characterization of this region. The ICAM-2 promoter is TATA-less, and transcription in endothelial cells initiates at four sites. Reporter gene expression directed by the promoter was 125-fold greater than vector alone in bovine aortic endothelial cells but less than 2-fold vector alone in non-endothelial (COS) cells, confirming that specificity in vivo was paralleled in vitro. The addition of 2.7 kbp of 5-flanking region to the 0.33-kbp fragment had no effect on promoter activity or specificity. The mutation of an Sp1 motif centered at base pair ؊194 or an eight-base pair palindrome at ؊268 each reduced promoter activity by 70%. Mutation of GATA motifs at ؊145 and ؊53 reduced promoter activity by 78 and 61%, respectively. Specific binding of bovine aortic endothelial cells nuclear proteins to the Sp1 and GATA sites was demonstrated by gel shift analysis. Promoter activity in COS cells was transactivated 3-4-fold by overexpression of GATA-2. The results presented here suggest that transcription from the ICAM-2 promoter in endothelial cells is regulated by the interplay of several positive-acting factors and provide the basis for further analysis of endothelial-specific gene expression.

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“…In normal tissue, ICAM-2 is expressed at low levels and only by a subset of leukocytes and vascular endothelium. The functions of this CAM as a co-stimulatory signal for T cell stimulation, 50,51 in mediating neutrophil adhesion and migration through endothelial monolayers have been well described. [52][53][54][55] Several additional functions for ICAM-2 have been described for specific cell types.…”

Section: "Connection" Between Cams and The Actin Cytoskeletal Networkmentioning

confidence: 99%

Cell adhesion molecules as targets for therapy of neuroblastoma

Yoon¹,

Danks²

2009

Cancer Biology & Therapy

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ICAM‐2 Provides a Costimulatory Signal for T Cell Stimulation by Allogeneic Class II MHC

Cited by 13 publications

References 26 publications

Leflunomide inhibits transendothelial migration of peripheral blood mononuclear cells

Leflunomide inhibits transendothelial migration of peripheral blood mononuclear cells

The Human ICAM-2 Promoter is Endothelial Cell-specific in Vitro and in Vivo and Contains Critical Sp1 and GATA Binding Sites

Cell adhesion molecules as targets for therapy of neuroblastoma

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