??4 Integrin in Islet Allograft Rejection1

Stegall, Mark D.; Dean, Patrick G.; Ninova, Dora; Cohen, Ari J.; Shepard, G; Gup, Carol; Gill, Ronald G.

doi:10.1097/00007890-200106150-00011

Cited by 18 publications

(18 citation statements)

References 33 publications

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“…The reason for the lack of effect of CS1 peptide on either the degree of insulitis or the onset of diabetes is unclear but the difference may be that in the islet allograft setting the lymphocytes are not activated at the beginning of treatment while in the autoimmune diabetes setting the lymphocytes are already activated. Similarly, we have previously shown that treatment with mAbs against a4-integrin (PS/2) prevents in vitro responses to alloantigen [20]. Other studies have suggested that other mAbs against a4-integrin (R1.2) do not block in vitro responses to islet antigens [8].…”

Section: Groupsupporting

confidence: 57%

“…Therefore, the in vivo effects of adhesion molecule blockade, with monoclonal antibodies or with peptide inhibitors, may be quite complex. We previously have shown that treatment with CS1 peptide prevents islet allograft rejection in mice by preventing lymphocyte homing to the graft [20]. The reason for the lack of effect of CS1 peptide on either the degree of insulitis or the onset of diabetes is unclear but the difference may be that in the islet allograft setting the lymphocytes are not activated at the beginning of treatment while in the autoimmune diabetes setting the lymphocytes are already activated.…”

Section: Groupmentioning

confidence: 99%

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Immunomodulation through inhibition of multiple adhesion molecules generates resistance to autoimmune diabetes in NOD mice

Ninova

Dean

Stegall

2004

Journal of Autoimmunity

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Section: Groupsupporting

confidence: 57%

Section: Groupmentioning

confidence: 99%

Immunomodulation through inhibition of multiple adhesion molecules generates resistance to autoimmune diabetes in NOD mice

Ninova

Dean

Stegall

2004

Journal of Autoimmunity

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“…Donor Balb/c islets were transduced with either Ad-XIAP or Ad-LacZ and transplanted under the kidney capsule of CBA recipients. Remarkably, only the XIAPexpressing islet transplants were found to persist beyond the normal range for islet allograft rejection of 10 -24 days in this model (21). In fact, 9 of 10 recipients of XIAPexpressing islet allografts maintained normoglycemia until the animals were killed between days 45 and 72 posttransplant (Fig.…”

Section: Resultsmentioning

confidence: 66%

The X-Linked Inhibitor of Apoptosis Protein Enhances Survival of Murine Islet Allografts

et al. 2005

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Allotransplantation of pancreatic islets represents a promising approach to treat type 1 diabetes. Destruction of ␤-cells in islet allografts involves multiple immune mechanisms that lead to activation of caspases and apoptotic cell death. The X-linked inhibitor of apoptosis (XIAP) inhibits apoptosis induced by a variety of triggers, primarily by preventing the activation of caspases. To determine whether XIAP would protect ␤-cells from apoptosis, we used a recombinant adenovirus to overexpress XIAP in transformed murine ␤-cells and in freshly isolated islets. In vitro cytokine-induced ␤-cell death was decreased to baseline levels in XIAPtransduced MIN-6 and NIT-1 cell lines compared with controls. To evaluate the potential of XIAP overexpression to prevent in vivo allogeneic graft rejection, we transduced Balb/c islets ex vivo with XIAP before transplantation into CBA mice with streptozotocin-induced diabetes. We observed that almost all mice receiving allografts of XIAP-expressing islets maintained normoglycemia until the experiment was terminated (45-72 days posttransplant), whereas control mice receiving islets transduced with adenovirus expressing LacZ were hyperglycemic by ϳ17 days posttransplantation due to graft rejection. Immunohistochemistry revealed preservation of ␤-cells and clearance of infiltrating immune cells in the XIAP-expressing islet grafts. The in vitro allogeneic response of splenocytes isolated from recipients of XIAP-expressing grafts 8 weeks posttransplant was similar to that seen in nonprimed allogeneic mice, suggesting that XIAP overexpression may lead to the acceptance of islet allografts in diabetic recipients. Long-term protection of islet allografts by XIAP overexpression may enhance the survival of islet transplants in diabetes. Diabetes 54:2533-2540, 2005

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“…In an experimental autoimmune encephalomyelitis model, MK1.9 reduced disease severity (54). Another VCAM-1 Ab, MK2.7, allowed long-term islet allograft survival of .100 d with a survival rate of 75% of the islet grafts (55). In a mouse model of Crohn's disease, MK2.7 treatment yielded a 70% resolution of the acute inflammation (56).…”

Section: Discussionmentioning

confidence: 99%

An Antibody to the Sixth Ig-like Domain of VCAM-1 Inhibits Leukocyte Transendothelial Migration without Affecting Adhesion

Lee

Yoon

et al. 2012

The Journal of Immunology

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VCAM-1 plays a key role in leukocyte trafficking during inflammatory responses. However, molecular mechanisms underlying this function have not been clearly elucidated. In this study, using phage display technology, we developed a rabbit/human chimeric VCAM-1 Ab, termed VCAM-1 domain 6 (VCAM-1-D6), which specifically recognizes aa 511–599 within the sixth Ig-like domain. We report that the VCAM-1-D6 Ab blocked U937 cell transmigration across activated HUVECs but did not alter adhesion of U937 cells to the HUVECs. We also demonstrate that VCAM-1-D6 does not alter TNF-α–stimulated endothelial cell chemokine or cytokine production. Furthermore, through in vivo efficacy testing using a mouse islet allograft model, we demonstrate that VCAM-1-D6 significantly alleviates allograft rejection by blocking leukocyte infiltration to the grafted islets. Taken together, our results suggest that the VCAM-1-D6 Ab may block VCAM-1–mediated inflammation and could be a useful tool in treating inflammatory diseases.

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??4 Integrin in Islet Allograft Rejection1

Cited by 18 publications

References 33 publications

Immunomodulation through inhibition of multiple adhesion molecules generates resistance to autoimmune diabetes in NOD mice

Immunomodulation through inhibition of multiple adhesion molecules generates resistance to autoimmune diabetes in NOD mice

The X-Linked Inhibitor of Apoptosis Protein Enhances Survival of Murine Islet Allografts

An Antibody to the Sixth Ig-like Domain of VCAM-1 Inhibits Leukocyte Transendothelial Migration without Affecting Adhesion

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