Chemokine and chemokine receptor expression analysis in target organs of acute graft-versus-host disease

A. Bouazzaoui, E. Spacenko, G. Mueller, S. Miklos, E. Huber, E. Holler, R. Andreesen, G. C. Hildebrandt

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic bone marrow transplantation (allo-BMT), and infiltration of donor leukocytes into aGVHD target organs is partially orchestrated by chemokines. Using a murine BMT model, the expression of 30 chemokines or chemokine receptors in the lung, liver, gut and tongue was analyzed using real-time PCR at 1, 2, 3 and 6 weeks after BMT during the development of clinical aGVHD and target organ histopathology. CXCL9-11 expression was linked to elevated expression of CXCR3 in the gut, lung and tongue. In contrast, hepatic CXCR3 expression was not changed, whereas a clear association was seen for CXCL16 and CXCR6 expression. An elevated intestinal CCL3 expression 1 week after allo-BMT was associated with an increased expression of CCR5 but not CCR1 or CCR3, and in the lung and liver CCL3-CCL5 expression was associated with increases in CCR1 and CCR5. Overexpression of CCL2, CCL8, CCL12 and their receptor CCR2 was found in the liver and lung, but not in the gut and tongue. On the basis of the differences in kinetics and organ distribution, more studies are required to better characterize specific targets within this network, as this will allow the development of novel preventive and therapeutic approaches by using single or multiple targeting reagents.

Original languageEnglish
Pages (from-to)687-701
Number of pages15
JournalGenes and Immunity
Volume10
Issue number8
DOIs
StatePublished - Dec 2009

Bibliographical note

Funding Information:
This work was support by the Deutsche Krebshilfe e.V., Project #106647. We thank the Biostatistician Dr Christoph Ehret (Department of Hematology and Oncology, University of Regensburg Medical Center) for his advice and assistance with the statistical analyses.

Keywords

  • Chemokine
  • Chemokine receptor
  • Graft-versus-host disease
  • Leukocyte recruitment
  • Stem cell transplantation

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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