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Early up-regulation of CXC-chemokine expression is associated with strong cellular immune responses to murine skin xenografts

Cited 8 time in Web of Science Cited 7 time in Scopus
Authors
Lee, Eun Mi; Park, Joon Oh; Kim, Donghee; Kim, Jae Young; Oh, Kook-Hwan; Park, Chung-Gyu; Oh, Byung Hee; Kim, Suhnggwon; Ahn, Curie
Issue Date
2006-06-14
Publisher
Blackwell Publishing
Citation
Xenotransplantation. 2006 Jul;13(4):328-36.
Keywords
AnimalsChemokine CCL5/genetics/immunologyChemokine CXCL10Chemokine CXCL9Chemokines, CXC/genetics/*immunologyFemaleGraft Rejection/immunologyImmunity, CellularMiceMice, Inbred BALB CMice, Inbred C57BLRatsReceptors, CXCR3Receptors, Chemokine/immunologySkin Transplantation/*immunologySpecific Pathogen-Free OrganismsTransplantation, Heterologous/*immunologyTransplantation, Homologous/immunologyTransplantation, Isogeneic/immunologyUp-Regulation
Abstract
BACKGROUND: The dynamic pattern of the cellular infiltration and mRNA expression of chemokines in rat-to-mouse skin xenografts were examined to gain an understanding of the possible role of chemokines in the stronger cellular immune responses to xenografts compared with the allo-response. METHODS: The mean survival time of the xenografts was approximately 2 days less than that of allografts (10.7 +/- 0.9 days vs. 8.9 +/- 0.7 days, P < 0.05). In comparison with the allografts, the xenografts were characterized by a very early infiltration of monocytes/macrophages (day 3) and a larger number of CD4+ and CD8+ cells, as well as neutrophil infiltration in the early phase (day 5), and larger number of CD8+ and CD11b+ cells, as well as macrophage infiltration, in the later phase (day 7). Xenografts showed stronger interferon (IFN)-inducible 10-kDa protein (IP-10) and monokine induced by IFN (MIG) mRNA expression levels, which appeared earlier than in the allografts. In the later phase, strong expression of regulated on activation, normal T cell expressed and secreted was observed. Cytokine mRNA expression in the xenografts could be summarized by higher expression of IFN-gamma, interleukin (IL)1beta, IL6, and transforming growth factor -beta1 mRNA than in the allografts. These results suggest that the early increased CXC-chemokine expression, such as IP-10 and MIG, which has been known to be mainly produced by macrophages, may play a critical role in the stronger cellular xenograft rejection compared with allograft rejection. Therefore, MIG antiserum or CXCR3 antiserum was administered to the rat skin-engrafted mice every other day until rejection. RESULTS: Compared with the control normal rabbit serum-treated mice, either the MIG antiserum- or CXCR3 antiserum-treated mice showed a delayed rejection of approximately 2 days (8.3 +/- 0.5 days vs. 10.6 +/- 0.5 days or 10.8 +/- 1.9 days, respectively, P < 0.05). CONCLUSION: Overall, these results suggest that the more aggressive rejection of xenografts compared with allografts is due to the earlier expression of CXC-chemokines, IP-10 and MIG, and subsequent adjuvant effects of proinflammatory cytokines.
ISSN
0908-665X (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16768726

http://hdl.handle.net/10371/28915
DOI
https://doi.org/10.1111/j.1399-3089.2006.00311.x
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College of Medicine/School of Medicine (의과대학/대학원)Microbiology (미생물학전공)Journal Papers (저널논문_미생물학전공)
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