title: Early expression of plasma CCL8 closely correlates with survival rate of acute graft-vs.-host disease in mice.
abstract: OBJECTIVE
  To elucidate the significance of early expression of CC-chemokine ligand motif 8 (CCL8) in mice with graft-vs.-host disease (GVHD), we investigated its induction mechanisms and correlation with overall survival rate in GVHD mice. Plasma CCL8 increases on day 5 of allogeneic transplantation, when signs of GVHD are barely detectable. Increase of allogeneic splenocytes in grafts exacerbates GVHD and leads to upregulation of plasma CCL8 on day 5. Overall survival is the gold standard in determining the severity of acute GVHD in mice, but the absence of clinical and/or pathological manifestations in the early phase make it difficult to estimate vital outcomes at this stage of allogeneic marrow transplantation.
  
  
  METHODS
  After lethal irradiation, BALB/c mice received bone marrow transplantation from C57BL/6 mice. Survival rate was monitored and clinical and pathological scores of GVHD were examined. Coculture of BALB/c-derived dendritic cells and C57BL/6-derived splenocytes was performed. CCL8 was measured by immunoassay.
  
  
  RESULTS
  The plasma CCL8 level at day 5 of transplantation was closely correlated with survival rate and clinical/pathological scores on day 14. In vitro study revealed that the BALB/c-derived dendritic cells expressed CCL8 upon stimulation of C57BL/6 CD4(+) T cells by cell interactions through major histocompatibility complex class II molecules.
  
  
  CONCLUSIONS
  These investigations indicate that early and preclinical expression of CCL8 in plasma predicts overall survival of GVHD mice. Together with an involvement of allo-recognition in CCL8 expression, it suggests that CCL8 plays an important role in GVHD pathology.
authors.affiliation: Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Japan. ymasaki@sapmed
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Akinobu
authors.initials: A
authors.lastname: Ota
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Hori
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Imai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sohma
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Hatakeyama
authors.forename: Natsuko
authors.initials: N
authors.lastname: Inazawa
authors.forename: Yoichi M
authors.initials: YM
authors.lastname: Ito
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsumi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kokai
mesh_terms: D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000401:mortality; D002450:Cell Communication / Q000276:immunology; D054412:Chemokine CCL8 / Q000096:biosynthesis* / Q000097:blood*; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology; D006086:Graft vs Host Disease / Q000401:mortality*; D051379:Mice; D023421:Models, Animal; D011379:Prognosis; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D015533:Transcriptional Activation; D014184:Transplantation, Homologous
chemical_list: C515454:Ccl8 protein, mouse; D054412:Chemokine CCL8