Macrophage inflammatory protein-2 (MIP-2)/CXCR2 blockade attenuates acute graft-versus-host disease while preserving graft-versus-leukemia activity

Kyung Ah Cho, So Youn Woo, Yoon Shin Park, Min Hwa Park, Kyung Ha Ryu

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Allogenic bone marrow transplantation (BMT), an important treatment for hematological malignancies, is often complicated by graft-versus-host disease (GVHD). Suppression of GVHD is associated with the unwanted diminishment of the graft-versus-leukemia (GVL) response. The aim of this study was to maintain the benefits of GVL during GVHD suppression through isolated blockade of T-cell migration factors. To this end, we developed a murine model of B-cell leukemia, which was treated with BMT to induce GVHD. Within this model, functional blockade of MIP-2/CXCR2 was analyzed by observing proteomic, histologic and clinical variables of GVHD manifestation. Luminex assay of collected tissue identified several cytokines [granulocyte colony-stimulating factor (G-CSF), keratinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2), and interleukin-23 (IL-23)] that were upregulated during GHVD, but reduced by neutralizing the MIP-2/CXCR2 axis. In addition, donor T-cell blockade of CXCR2 combined with recipient administration of anti-MIP-2 caused a significant decrease in GVHD while preserving the GVL response. We propose that blocking the MIP-2/CXCR2 axis represents a novel strategy to separate the toxicity of GVHD from the beneficial effects of GVL after allogenic BMT.

Original languageEnglish
Pages (from-to)558-564
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume426
Issue number4
DOIs
StatePublished - 5 Oct 2012

Bibliographical note

Funding Information:
This work was supported by the Korea Food and Drug Administration in 2011 [grant number 11172KFDA367 ]. There are no financial conflicts of interest.

Keywords

  • Bone marrow transplantation
  • CXCR2
  • Graft-versus-host disease
  • Graft-versus-leukemia
  • MIP-2

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