TY - JOUR
T1 - Alpha-1 Antitrypsin Treatment of Spontaneously Diabetic Nonobese Diabetic Mice Receiving Islet Allografts
AU - Pileggi, Antonello
AU - Molano, R. D.
AU - Song, S.
AU - Zahr, E.
AU - SanJose, S.
AU - Villate, S.
AU - Wasserfall, C.
AU - Ricordi, C.
AU - Atkinson, M. A.
AU - Inverardi, L.
PY - 2008/3/1
Y1 - 2008/3/1
N2 - Alpha-1 antitrypsin (AAT) is a serine protease inhibitor able to prevent diabetes onset in nonobese diabetic (NOD) mice and to prolong islet allograft survival in a nonautoimmune murine model. In this study, we explored the effect of chronic administration of human AAT (hAAT) on allogeneic (C57BL/6) islet graft survival in spontaneously diabetic female NOD mice. Mice received intraperitoneal treatment with saline, Prolastin (1 or 2 mg/mouse) or Aralast (2 mg/mouse) on days -1, 0, 3, 6, and 9. Saline-treated mice rejected the grafts 10.0 ± 2.5 days after transplantation (n = 9). Prolastin 1 mg (n = 9) and 2 mg (n = 3) resulted in rejection on 8.7 ± 1.4 (not significant) and 13.0 ± 4.3 days (P < .03), respectively. Aralast-treated mice showed prolongation of graft survival (13 ± 5.9 days; n = 5; P < .03). Notably, repeated administrations of either hAAT formulation led to sudden death of a proportion of treated animals. Collectively, our preliminary data indicate that prolongation of islet allograft survival in the stringent autoimmune diabetic NOD mouse model can be achieved with hAAT monotherapy. The death of a proportion of treated animals may be consequent to immunization to hAAT and lethal hypersensitivity. Interestingly, this phenomenon was not observed in a non-autoimmune mouse strain (C57BL/6) despite extended hAAT treatment (>100 days).
AB - Alpha-1 antitrypsin (AAT) is a serine protease inhibitor able to prevent diabetes onset in nonobese diabetic (NOD) mice and to prolong islet allograft survival in a nonautoimmune murine model. In this study, we explored the effect of chronic administration of human AAT (hAAT) on allogeneic (C57BL/6) islet graft survival in spontaneously diabetic female NOD mice. Mice received intraperitoneal treatment with saline, Prolastin (1 or 2 mg/mouse) or Aralast (2 mg/mouse) on days -1, 0, 3, 6, and 9. Saline-treated mice rejected the grafts 10.0 ± 2.5 days after transplantation (n = 9). Prolastin 1 mg (n = 9) and 2 mg (n = 3) resulted in rejection on 8.7 ± 1.4 (not significant) and 13.0 ± 4.3 days (P < .03), respectively. Aralast-treated mice showed prolongation of graft survival (13 ± 5.9 days; n = 5; P < .03). Notably, repeated administrations of either hAAT formulation led to sudden death of a proportion of treated animals. Collectively, our preliminary data indicate that prolongation of islet allograft survival in the stringent autoimmune diabetic NOD mouse model can be achieved with hAAT monotherapy. The death of a proportion of treated animals may be consequent to immunization to hAAT and lethal hypersensitivity. Interestingly, this phenomenon was not observed in a non-autoimmune mouse strain (C57BL/6) despite extended hAAT treatment (>100 days).
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U2 - 10.1016/j.transproceed.2008.02.010
DO - 10.1016/j.transproceed.2008.02.010
M3 - Article
C2 - 18374100
AN - SCOPUS:41049098117
VL - 40
SP - 457
EP - 458
JO - Transplantation Proceedings
JF - Transplantation Proceedings
SN - 0041-1345
IS - 2
ER -