title: Early up-regulation of CXC-chemokine expression is associated with strong cellular immune responses to murine skin xenografts.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Xenotransplantation Research Center and Transplantation Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Lee
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Donghee
authors.initials: D
authors.lastname: Kim
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Kook-Hwan
authors.initials: KH
authors.lastname: Oh
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Byung Hee
authors.initials: BH
authors.lastname: Oh
authors.forename: Suhnggwon
authors.initials: S
authors.lastname: Kim
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
mesh_terms: D000818:Animals; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D014183:Transplantation, Heterologous / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology; D014185:Transplantation, Isogeneic / Q000276:immunology; D015854:Up-Regulation
chemical_list: C111954:CXC chemokine Mig; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; C515189:Cxcr3 protein, rat; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine