Integrin signaling via RGD peptides and anti-beta1 antibodies confers resistance to apoptosis in islets of Langerhans.
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 beta-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-beta1 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-beta1 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.
Pinkse
Gabrielle G M
GG
Department of Pathology, Leiden University Medical Center, Netherlands. g.g.m.pinkse@lumc.nl
Bouwman
Wendy P
WP
Jiawan-Lalai
Reshma
R
Terpstra
O T
OT
Bruijn
Jan A
JA
de Heer
Emile
E
D000818:Animals; D023102:Anoikis / Q000502:physiology*; D000906:Antibodies / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D019012:Integrin beta1 / Q000276:immunology* / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009842:Oligopeptides / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
D000906:Antibodies; D019012:Integrin beta1; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases