Differential expression of chemokines and chemokine receptors in murine islet allografts: The role of CCR2 and CCR5 signaling pathways

Bernd Schröppel, Nan Zhang, Peng Chen, Weiping Zang, Dongmei Chen, Kelly L. Hudkins, William A. Kuziel, Randall Sung, Jonathan S. Bromberg, Barbara Murphy

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Chemokines and their receptors play a pivotal role in the initiation and amplification of the immune response. Investigated was their differential expression after syngeneic and allogeneic islet transplantation. During the 7 d after transplantation, the chemokines MCP-1, MCP-2, RANTES, MIG, IP-10, I-TAC, and two CC chemokine receptors CCR2 and CCR5 were highly expressed in allografts when compared with isografts. Disrupting the CCR2 and CCR5 pathways individually resulted in prolongation of the survival time 16.1 ± 0.4 and 15.8 ± 0.9 d, respectively, of fully major histocompatibility complex-mismatched islet grafts compared with wild-type controls (11.2 ± 1.0 d). Blockade of both receptors had no synergistic effect. Rapamycin-treated wild-type recipients rejected their grafts at 17.4 ± 2.2 d, in contrast to rapamycin-treated CCR2-/- recipients at 38 ± 8.6 d (P = 0.025). The disruption of the CCR2 and CCR5 signaling, alone or in combination, moderately prolong islet allograft survival. However, the combination of low-dose immunosuppression and targeting of CCR2 greatly augmented islet graft survival.

Original languageEnglish
Pages (from-to)1853-1861
Number of pages9
JournalJournal of the American Society of Nephrology : JASN
Volume15
Issue number7
DOIs
StatePublished - Jul 2004

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