title: Differential chemokine gene expression in corneal transplant rejection.
abstract: OBJECTIVE
  To evaluate the differential gene expression of chemokines after corneal transplantation and to determine the chemokines associated with allograft rejection.
  
  
  METHODS
  Orthotopic mouse corneal transplantation was performed in two fully mismatched-strain combinations using C57BL/6 (H-2b) and BALB/c (H-2d) mice as recipients and BALB/c and C57BL/6 mice as donors. Normal nonsurgical eyes served as negative control specimens and syngeneic transplants (isografts) as control specimens for the alloimmune response. Chemokine gene expression in accepted and rejected allografts and appropriate control specimens was determined by a multiprobe RNase protection assay system.
  
  
  RESULTS
  In eyes with rejected allografts, there was overexpression of regulated on activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-2, and monocyte chemotactic protein (MCP)-1 in both C57BL/6 and BALB/c recipients. In addition, C57BL/6 eyes with rejected allografts expressed very high levels of interferon-gamma-inducible protein of 10 kDa (IP-10) mRNA, in contrast to BALB/c eyes with rejected allografts, in which IP-10 expression remained very low. In contrast, lymphotactin gene expression increased only slightly in rejected allografts, and eotaxin mRNA, which was also detected in normal eyes, remained unchanged among isograft and allograft groups. T-cell activation gene (TCA)-3 mRNA was not detected in any of the assayed eyes.
  
  
  CONCLUSIONS
  Increased expression of mRNA for select chemokines of the CXC (alpha) and CC (beta) families is associated with corneal allograft rejection. Significantly elevated IP-10 gene expression in high-rejector C57BL/6, but not in low-rejector BALB/c, hosts suggests that differential activation of chemokines may be related to differences in alloimmune reactivity observed among different murine strains.
authors.affiliation: Laboratory of Immunology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yamagami
authors.forename: D
authors.initials: D
authors.lastname: Miyazaki
authors.forename: S J
authors.initials: SJ
authors.lastname: Ono
authors.forename: M R
authors.initials: MR
authors.lastname: Dana
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D003315:Cornea / Q000378:metabolism*; D016039:Corneal Transplantation; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics* / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger