Adhesion Molecules in Human Islet β-cells: De Novo Induction of ICAM-1 but Not LFA-3

Vives, Marta; Soldevila, Gloria; Alcalde, Laura; Lorenzo, C Di; Somoza, Nuria Rey; Pujol-Borrell, Ricardo

doi:10.2337/diab.40.11.1382

Cited by 27 publications

(14 citation statements)

References 25 publications

(31 reference statements)

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“…It has been shown that TNF-a can induce the expression of ICAM-1 on human islet B cells (20,21 ). This was confirmed on rat cells in the course of the present study.…”

Section: Discussionsupporting

confidence: 76%

“…Furthermore, the cytokine TNF-a has been shown to induce the expression of a CAM, the intercellular CAM-l (ICAM-1), on pancreatic endocrine B cells (20,21 ). Thus, in addition to allowing the attachment of cytotoxic lymphocytes, this cytokine might initiate islet dysfunction by the induction of unusual CAMs, with the resulting loss of islet cell type segregation, or by modifying the expression of constitutive CAMs responsible for normal cell type adhesion and segregation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor necrosis factor-alpha modifies adhesion properties of rat islet B cells.

Cirulli

Halban²,

Rouiller³

1993

J. Clin. Invest.

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The characteristic three-dimensional cell type organization of islets of Langerhans is perturbed in animal models of diabetes, suggesting that it may be important for islet function. Rat islet cells in culture are able to form aggregates with an architecture similar to native islets (pseudoislets), thus providing a good model to study the molecular basis of islet architecture and its role in islet function. Sorted islet B cells and non-B cells were permanently labeled with two different fluorescent dyes (DiO and DiI), mixed, and allowed to form aggregates during a 5-d culture in the presence or absence of TNF-a (100 U/ml), a cytokine suggested to be implicated in the early physiological events leading to insulin-dependent diabetes mellitus. Confocal microscopy of aggregates revealed that TNF-a reversibly perturbs the typical segregation between B and non-B cells. Insulin secretion, was altered in the disorganized aggregates, and returned towards normal when pseudoislets had regained their typical architecture. The homotypic adhesion properties of sorted B and non-B cells cultured for 20 h in the presence or absence of TNF-a were studied in a short term aggregation assay. TNF-a induced a significant rise in Ca2"-independent adhesion of B cells (from 24±1.1% to 44.3+1.2%; n = 4, P <0.001). These findings raise the possibility that the increased expression of Ca2"-independent adhesion molecules on B cells leads to altered islet architecture, which might be a factor in the perturbation of islet function induced by TNF-a.

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“…It has been shown that TNF-a can induce the expression of ICAM-1 on human islet B cells (20,21 ). This was confirmed on rat cells in the course of the present study.…”

Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor-alpha modifies adhesion properties of rat islet B cells.

Cirulli

Halban²,

Rouiller³

1993

J. Clin. Invest.

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“…Previous experimental studies (36,37) demonstrated that pancreatic islet cells could express adhesion molecules, as well as MHC molecules, when stimulated by IFN-,y and/or TNF-a in vitro, suggesting the possible participation of the molecules in the pathogenesis of IDDM. Therefore, we analyzed two adhesion molecules, ICAM-1 and LFA-3, in IDDM pancreases.…”

Section: Discussionmentioning

confidence: 99%

Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients.

et al. 1993

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We examined pancreas biopsy specimens from 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients to elucidate the mechanism underlying beta cell destruction. Pancreas islets were seen in all patients and insulitis in eight patients. Infiltrating mononuclear cells consisted of CD4+T, CD8+T, B lymphocytes, and macrophages. Among them, CD8+T lymphocytes were predominant and macrophages followed. The expression of MHC class I antigens was increased in islet and endothelial cells in nine patients. MHC class II expression was increased in endothelial cells of the same patients. The expression of intercellular adhesion molecule-i was increased in endothelial cells in two of the nine patients with MHC hyperexpression; in one of them, lymphocyte functionassociated antigen-3 expression was also increased. Out of the eight patients with insulitis, seven showed MHC class I hyperexpression, whereas 2 of the 10 patients without insulitis showed the phenomenon (P < 0.05). The relation between insulitis and the hyperexpression of adhesion molecules was not evident. In conclusion, we revealed the close relation between CD8+T lymphocyte-predominant insulitis and MHC class I hyperexpression in islet cells. This suggests that infiltrating CD8 'T lymphocytes recognize islet autoantigens in association with increased MHC class I molecules and act as major effector cells in autoimmune response against islet cells in IDDM pancreases. The role of adhesion molecules in the pathogenesis of IDDM still remains to be elucidated. (J. Clin. Invest. 1993.

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“…The results of TAP-1 flow cytometry were clearly reproducible (CV < 10%). To assess better the distribution of TAP-1 in the cytoplasm of thyrocytes, monolayer cultures were also stained as described [19].…”

Section: Methodsmentioning

confidence: 99%

Hyperexpression of transporter in antigen processing-1 (TAP-1) in thyroid glands affected by autoimmunity: a contributory factor to the breach of tolerance to thyroid antigens?

Sospedra

Armengol

Ashhab

et al. 1997

Clinical and Experimental Immunology

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SUMMARYAccording to the 'aberrant HLA expression' hypothesis, endocrine autoimmunity is driven by presentation of self antigens by target cells over-expressing HLA molecules. In autoimmune thyroid diseases (AITD), thyroid follicular cells (thyrocytes) over-express HLA class I and HLA class II molecules. Since efficient presentation of endogenous peptides via class I requires transporters that translocate endogenous peptides from the cytoplasm to the endoplasmic reticulum, i.e. transporters associated with antigen processing (TAP) -1 and -2, the capability of thyrocytes to express TAP and whether TAP is hyperexpressed in AITD glands are issues relevant to the above hypothesis. Results from immunofluorescence and Northern blotting studies on primary thyrocyte cultures and on a thyroid cell line demonstrate that thyrocytes express constitutively TAP-1 at a low level, and that this expression is readily induced by interferon-gamma (IFN-g) and to a lesser extent by IFN-a. In AITD, but not in non-autoimmune glands, thyrocytes hyperexpress TAP-1, as demonstrated by both immunohistopathology and flow cytometry. The cytokine pattern does not bear, as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), a clear relationship with TAP-1 expression. These results have broad implications and suggest that the core concept of the 'aberrant HLA expression' hypothesis of endocrine autoimmunity could be incorporated in the currently prevailing view of 'autoimmunity by breach of peripheral tolerance'.

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Adhesion Molecules in Human Islet β-cells: De Novo Induction of ICAM-1 but Not LFA-3

Cited by 27 publications

References 25 publications

Tumor necrosis factor-alpha modifies adhesion properties of rat islet B cells.

Tumor necrosis factor-alpha modifies adhesion properties of rat islet B cells.

Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients.

Hyperexpression of transporter in antigen processing-1 (TAP-1) in thyroid glands affected by autoimmunity: a contributory factor to the breach of tolerance to thyroid antigens?

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