Blocking the CC chemokine receptor 5 pathway by antisense peptide nucleic acid prolongs islet allograft survival.
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 Peptide nucleic acid (PNA) is a nucleic acid analog in which the sugar phosphate backbone of natural nucleic acid has been replaced by a synthetic peptide backbone.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.
Yang
L
L
Department of Transplantation, the First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China. yanglei72@medmail.com.cn
Liu
Y F
YF
Wu
G
G
Zhang
J L
JL
Wang
F S
FS
Fu
D Z
DZ
Zhao
G H
GH
Li
T M
TM
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
D065100:CCR5 Receptor Antagonists; D017931:DNA Primers; D016373:DNA, Antisense; D020135:Peptide Nucleic Acids; D019713:Receptors, CCR5