Modest Effects of Fas-Ligand and Heme Oxygenase-1 Double Transgenic Mouse Islets on Transplantation Outcomes

Abstract

Interactions of Fas with its ligand (FasL) play an important role in the maintenance of immunologic homeostasis and peripheral tolerance. Heme oxygenase-1 (HO-1) is a protein capable of cytoprotection via radical scavenging and apoptosis prevention. The aim of this study was to test whether overexpression of FasL and HO-1 in murine islets resulted in cell protection and improved functional performance after transplantation. We first generated FasL and HO-1 double transgenic mice to investigate the protective effect of transgenic islets on transplantation. Islets were isolated from FasL and HO-1 double transgenic and nontransgenic Balb/c mice, for transplantation of 300 islets under the left kidney capsule of each streptozotocin-diabetic Balb/c mouse. During 6 weeks after transplantation, the blood glucose gradually decreased in recipients of double transgenic and nontransgenic islets. However, the decrease in blood glucose was more pronounced in the former (450 +/- 16 mg/dL at day 0 to 302 +/- 55 mg/dL at day 42; P =.01) than the latter (468 +/- 17 mg/dL at day 0 to 379 +/- 71 mg/dL at day 42; P =.24). The areas under the curve of intraperitoneal glucose tolerance tests at 2, 4, and 6 weeks were not significantly different between recipients of double transgenic and nontransgenic islets. The body weight increased in recipients of double transgenic islets (21.1 +/- 1.4 g at day 0 to 26.2 +/- 0.8 g at day 42; P =.0002) and nontransgenic islets (21.0 +/- 1.4 g at day 0 to 25.1 +/- 0.4 g at day 42; P =.0448). Our data suggested modest beneficial effects of transgenic islets with FasL and HO-1 overexpression for transplantation.