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

作者：Cho Kyung Ah; Woo So Youn; Park Yoon Shin; Park Min Hwa; Ryu Kyung Ha^*

来源：Biochemical and Biophysical Research Communications, 2012, 426(4): 558-564.

DOI：10.1016/j.bbrc.2012.08.126

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

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.

• 出版日期2012-10-5