title: Blocking the CC chemokine receptor 5 pathway by antisense peptide nucleic acid prolongs islet allograft survival.
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 Peptide nucleic acid (PNA) is a nucleic acid analog in which the sugar phosphate backbone of natural nucleic acid has been replaced by a synthetic peptide backbone.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.
authors.affiliation: Department of Transplantation, the First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China. yanglei72@medmail.com.cn
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: Y F
authors.initials: YF
authors.lastname: Liu
authors.forename: G
authors.initials: G
authors.lastname: Wu
authors.forename: J L
authors.initials: JL
authors.lastname: Zhang
authors.forename: F S
authors.initials: FS
authors.lastname: Wang
authors.forename: D Z
authors.initials: DZ
authors.lastname: Fu
authors.forename: G H
authors.initials: GH
authors.lastname: Zhao
authors.forename: T M
authors.initials: TM
authors.lastname: Li
mesh_terms: D000818:Animals; D065100:CCR5 Receptor Antagonists; D017931:DNA Primers; D016373:DNA, Antisense / Q000494:pharmacology*; D006084:Graft Rejection / Q000517:prevention & control; D016381:Islets of Langerhans Transplantation / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D020135:Peptide Nucleic Acids / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000502:physiology; D014184:Transplantation, Homologous
chemical_list: D065100:CCR5 Receptor Antagonists; D017931:DNA Primers; D016373:DNA, Antisense; D020135:Peptide Nucleic Acids; D019713:Receptors, CCR5