Chemokine expression in nerve allografts

Rajiv Midha, Catherine A. Munro, Vankayalapati Ramakrishna, Takeshi Matsuyama, Reginald M. Gorczynski, Jason H. Huang, Eric L. Zager, Jacob Schwarz, James N. Campbell, P. David Adelson, David G. Kline

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: Chemokines (chemoattractant cytokines) play a major role in trafficking of cells to areas of inflammation. Infiltration of allograft tissues by immunocompetent cells is critical for rejection of donor tissues. The role of chemokines in nerve allograft rejection is not clear. We hypothesized that chemokines are responsible for attracting macrophages and T lymphocytes into nerve allograft tissue, initiating the graft rejection process. METHODS: Lewis rats received 4-cm-long peroneal nerve allografts and isografts from ACI and Lewis rats, respectively. Twelve hours to 10 days after transplantation, grafts were removed and total cellular ribonucleic acid was extracted. Intragraft gene expression of several chemokines (cytokine-induced neutrophil chemoattractant, macrophage inflammatory protein [MIP]-2, monocyte chemoattractant protein-1, MIP-1α, and regulated upon activation normal T-cell expressed and secreted [RANTES]) were analyzed by reverse transcription-polymerase chain reaction. RESULTS: The cytokine-induced neutrophil chemoattractant was expressed in allografts and isografts at early time points (12 h to 6 d). Monocyte chemoattractant protein-1 messenger ribonucleic acid expression was similarly high in both isografts and allografts from 12 hours until 8 days after transplantation. MIP-1α, MIP-2, and RANTES were expressed only in allografts. Kinetics of the neutrophil (MIP-2) and macrophage (MIP-1α) chemokines revealed an early onset (12-24 h), a plateau from 1 to 4 days, and expression abruptly declining by Day 6. The lymphocyte chemoattractant RANTES had delayed kinetics, with a rise at Day 3, a peak at Day 4, and a gradual decline. CONCLUSION: Induction of specific chemokine genes precedes nerve allograft infiltration by immunocompetent cells. MIP-1α, MIP-2, and RANTES may be responsible for recruiting macrophages, granulocytes, and lymphocytes, respectively, to the rejecting allograft. In future studies, blockade of these specific chemokines or their receptors may prove to delay or prevent nerve allograft rejection.

Original languageEnglish (US)
Pages (from-to)1472-1479
Number of pages8
JournalNeurosurgery
Volume54
Issue number6
DOIs
StatePublished - Jun 2004
Externally publishedYes

Keywords

  • Chemokines
  • Cytokine-induced neutrophil chemoattractant
  • Macrophage inflammatory protein
  • Monocyte chemoattractant protein
  • Nerve allografts
  • RANTES

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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  • Cite this

    Midha, R., Munro, C. A., Ramakrishna, V., Matsuyama, T., Gorczynski, R. M., Huang, J. H., Zager, E. L., Schwarz, J., Campbell, J. N., Adelson, P. D., & Kline, D. G. (2004). Chemokine expression in nerve allografts. Neurosurgery, 54(6), 1472-1479. https://doi.org/10.1227/01.NEU.0000125544.46576.76