Document Detail

Prolongation of rat islet allograft survival by treatment with monoclonal antibodies against VLA-4 and LFA-1.
MedLine Citation:
PMID:  7624946     Owner:  NLM     Status:  MEDLINE    
In this study, we investigated the effects of treatment with monoclonal antibodies against the VLA-4 and LFA-1 adhesion molecules on rat islet allograft rejection. TA-2 and TA-3 are function-blocking mAb against rat VLA-4 and LFA-1, respectively. Lewis rats were made diabetic (plasma glucose levels > 22.2 mmol/L) with streptozotocin. One week later, 1500 freshly isolated Wistar Furth rat islets were transplanted under the left kidney capsule of each rat. Monoclonal antibodies were administered intravenously at a dosage of 2 mg on the day of islet transplantation and then intraperitoneally every second day for 3 weeks or until graft rejection. Plasma glucose levels were monitored at least 3 times a week and blood leukocyte counts were monitored every 4 days. Rejection was defined as 2 plasma glucose levels > 11.1 mmol/L. Mean graft survival times in untreated and control mAb-treated rats were 5.3 and 6.0 days, respectively. Treatment with anti-VLA-4 or anti-LFA-1 resulted in only modest prolongation of mean graft survival time (9.3 and 7.4 days, respectively). However, treatment with the combination of anti-VLA-4 plus anti-LFA-1 resulted in long-term (i.e., 60-day) graft survival in 5 of 7 rats. Graft nephrectomy and histology confirmed islet graft survival at 60 days. A second Wistar Furth rat islet graft under the opposite renal capsule after graft nephrectomy did not show full tolerance; however, the function of the second graft was significantly prolonged without any immunosuppression. Combined blockade of VLA-4 and LFA-1 also markedly prolonged islet graft survival when islets were transplanted via the portal vein. In conclusion, both VLA-4 and LFA-1 play a role in islet allograft rejection and blockade of both prevents or greatly delays graft rejection.
H Yang; T B Issekutz; J R Wright
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  60     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  1995 Jul 
Date Detail:
Created Date:  1995-08-31     Completed Date:  1995-08-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  71-6     Citation Subset:  IM    
Department of Pathology, Izaak Walton Killam Children's Hospital, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada.
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MeSH Terms
Antibodies, Monoclonal / therapeutic use*
Diabetes Mellitus, Experimental / surgery
Graft Rejection / prevention & control
Graft Survival / drug effects*
Islets of Langerhans / pathology
Islets of Langerhans Transplantation*
Lymphocyte Function-Associated Antigen-1 / immunology*
Rats, Inbred Lew
Rats, Wistar
Receptors, Very Late Antigen / immunology*
Transplantation, Homologous
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Lymphocyte Function-Associated Antigen-1; 0/Receptors, Very Late Antigen

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