HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pinkse, G. G.M. Articles by de Heer, E. Search for Related Content PubMed PubMed Citation Articles by Pinkse, G. G.M. Articles by de Heer, E. Social Bookmarking                What's this?

Integrin Signaling via RGD Peptides and Anti-ß1 Antibodies Confers Resistance to Apoptosis in Islets of Langerhans

¹ Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
² Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands

Address correspondence and reprint requests to G.G.M. Pinkse, Department of Immunohematology and Blood Transfusion, E3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, Netherlands. E-mail: g.g.m.pinkse{at}lumc.nl

Key Words: ECM, extracellular matrix • ILK, integrin-linked kinase • polyHEMA, polyhydroxyethylmethacrylate • RGD, argenin-glycin-aspartic acid

Islet transplantation is associated with a high rate of early graft failure caused by early immune attack and poor functionality of islets. Apoptosis of islet cells appears soon after islet isolation and primarily involves the ß-cell. The purpose of this study was to determine the effect of ligation to extracellular matrix (ECM) proteins on survival of the islets of Langerhans following islet isolation. Islets that had been cultured for 24 h on collagen type I showed an islet survival of 59.7 ± 8.7%, while islets that had been cultured on collagen type IV and laminin showed an islet survival of 88.6 ± 10.3 and 94.3 ± 5.6%, respectively. Islets that had been pretreated with anti-ß1 antibodies and argenin-glycin-aspartic acid (RGD) peptides showed a decrease in the level of apoptosis by a factor of 2.5 and 3.1, respectively, and an increase of phospho-Akt Ser 473 activity by a factor of 3.1 and 2.9, respectively, compared with untreated islets. When detached from their natural ECM surrounding in the pancreas, islet cells undergo apoptosis, unless islets are cultured on collagen IV or laminin or treated with anti-ß1 integrin antibodies or RGD peptides to mimic ECM ligation. These results indicate that inhibition of anoikis may offer opportunities to improve function and viability of islet cells.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?