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Alpha-1 antitrypsin treatment of spontaneously diabetic nonobese diabetic mice receiving islet allografts.

Abstract：

: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).

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Pileggi A,Molano RD,Song S,Zahr E,SanJose S,Villate S,Wasserfall C,Ricordi C,Atkinson MA,Inverardi L

doi

10.1016/j.transproceed.2008.02.010

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

457-8

issue

2

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(08)00119-X

journal_volume

40

pub_type

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