CCR5 blockade in combination with cyclosporine increased cardiac graft survival and generated alternatively activated macrophages in primates

Jun Li, Gang Chen, Ping Ye, Sihua Wang, Kailun Zhang, Wenhao Chen, Stanislaw M. Stepkowski, Junhua Li, Shan Zhong, Jiahong Xia

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Maraviroc (MVC), a specific antagonist of CCR5 expressed on macrophages and activated T cells, may modulate inflammation and may be useful in patients with HIV infection. In this study we used nonhuman primates to examine the effect and mechanism of MVC alone or in combination with cyclosporine (CsA) to prolong cardiac allograft survivals. In an established rhesus monkey cardiac allograft model, recipients treated with MVC plus CsA showed significantly prolonged survival of heart allografts (>240 d, p < 0.001). These in vivo results in the MVC/CsA group correlated with delayed alloantibody response and markedly decreased graft infiltration by CCR5+, CD4+, CD8 +, and CD68+ cells (p < 0.05), as compared with other groups. Furthermore, grafts from the MVC/CsA group had elevated numbers of alternatively activated macrophages (AAMs) and the expression of peroxisome proliferator-activated receptor γ (PPARγ). Blockade of PPARγ abrogated the prolonged allograft survival (median survival time, 45 d) and the upregulated AAMs in MVC/CsA-treated recipients. In conclusion, MVC/CsA protects cardiac allograft in primates and this effect is associated with generating AAMs through activation of the PPARγ nuclear receptor.

Original languageEnglish (US)
Pages (from-to)3753-3761
Number of pages9
JournalJournal of Immunology
Volume186
Issue number6
DOIs
StatePublished - Mar 15 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'CCR5 blockade in combination with cyclosporine increased cardiac graft survival and generated alternatively activated macrophages in primates'. Together they form a unique fingerprint.

Cite this