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Updated: Jul 17, 2026
Transplantation of Pancreatic Islets Into the Kidney Capsule of Diabetic Mice
Published on: October 31, 2007
Blocking the CC chemokine receptor 5 pathway by antisense peptide nucleic acid prolongs islet allograft survival
1Department of Transplantation, the First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China. yanglei72@medmail.com.cn
Abstract:
Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. The CC chemokine receptor 5 (CCR5) is the receptor for the proinflammatory chemokines and plays an important role in islet allograft rejection. Peptide nucleic acid (PNA) is a nucleic acid analog in which the sugar phosphate backbone of natural nucleic acid has been replaced by a synthetic peptide backbone. Studies indicate that PNA inhibits both transcription and translation of targeted genes. Fullly major histocompatibility complex (MHC)-mismatched murine islet transplant models were used to test the in vivo effect of PNA CCR5 by targeting CCR5 in acute allograft rejection. PNA CCR5-treated recipients demonstrated significant prolongation (12.0 +/- 1.75 days) of functional allograft survival compared with saline (6.5 +/- 0.58 days)- or PNA mismatch-treated recipients (6.5 +/- 0.50 days). The PNA CCR5 blocked the expression of CCR5 in spleen CD3+ T cells. Lymphocytes from PNA CCR5-treated mice exhibited a reduced degree of proliferation comparable to that of saline- and PNA mismatch-treated mice. The present study indicated that PNA CCR5 has a substantial therapeutic effect to inhibit acute allograft rejection.
Insights
Peptide nucleic acid targeting CC chemokine receptor 5 (CCR5) significantly prolonged islet allograft survival in mice. This PNA CCR5 therapy reduced T cell activity, offering a potential strategy to inhibit acute allograft rejection.
Area of Science:
- Immunology
- Transplantation immunology
- Molecular biology
Background:
- Chemokines regulate leukocyte function and are implicated in islet allograft rejection.
- CC chemokine receptor 5 (CCR5) is a key mediator in inflammatory responses and allograft rejection.
- Peptide nucleic acid (PNA) is a synthetic nucleic acid analog that can inhibit gene transcription and translation.
Purpose of the Study:
- To investigate the in vivo therapeutic effect of PNA targeting CCR5 in a murine model of acute allograft rejection.
- To assess the impact of PNA CCR5 on allograft survival and immune cell function.
Main Methods:
- Utilized major histocompatibility complex (MHC)-mismatched murine islet transplant models.
- Administered PNA CCR5 to recipients and evaluated allograft survival duration.
- Analyzed CCR5 expression in spleen CD3+ T cells and measured lymphocyte proliferation.
Main Results:
- PNA CCR5 treatment significantly prolonged functional allograft survival (12.0 +/- 1.75 days) compared to control groups (6.5 +/- 0.58 and 6.5 +/- 0.50 days).
- PNA CCR5 effectively blocked CCR5 expression in spleen CD3+ T cells.
- Lymphocyte proliferation was reduced in PNA CCR5-treated mice.
Conclusions:
- PNA CCR5 demonstrates substantial therapeutic efficacy in inhibiting acute allograft rejection.
- Targeting CCR5 with PNA offers a promising approach for managing transplant rejection.
- Further research into PNA-based therapies for transplantation is warranted.
