title: Ly6C(+) monocytes are extrahepatic precursors of hepatic stellate cells in the injured liver of mice.
abstract: OBJECTIVE
  We previously reported that hepatic stellate cells (HpSCs) are of hematopoietic origin in liver injury. However, the immediate precursors of HpSCs remain unknown. This study was conducted to elucidate whether terminally differentiated blood cells can differentiate into HpSCs.
  
  
  METHODS
  We adoptively transferred a variety of cells isolated from enhanced green fluorescent protein (EGFP)-transgenic mice into carbon tetrachloride (CCl(4))-treated nontransgenic mice twice weekly for 2 weeks. We examined the presence of EGFP(+) HpSCs in the injured liver using immunofluorescence analysis.
  
  
  RESULTS
  Monocytes, neutrophils, eosinophils, B cells, or T cells from EGFP mice were transferred into CCl(4)-treated mice. Thirty percent of EGFP(+) cells in the livers of mice given Ly6C(high)c-kit(-) monocytes were negative for CD45, but were positive for glial fibrillary acidic protein, desmin, CD146, ADAMTS13, and α-smooth muscle actin, well-known markers of HpSCs. EGFP(+)CD45(-) cells were predominantly positive for glial fibrillary acidic protein. Although 48% of EGFP(+) cells were positive for procollagen type I, half of them were CD45(-). In the livers of mice given neutrophils, eosinophils, B cells, or T cells, all of the EGFP(+) cells were CD45(+). The majority of EGFP(+) cells in the nonparenchymal cell fraction purified from the livers of mice given Ly6C(high)c-kit(-) monocytes contained lipid droplets and were positive for glial fibrillary acidic protein, desmin, ADAMTS13, and procollagen type I. When Ly6C(+) monocyte-depleted peripheral blood total nucleated cells were adoptively transferred into CCl(4)-treated mice, we found no EGFP(+)CD45(-) cells in the liver.
  
  
  CONCLUSIONS
  These results suggest that Ly6C(+) monocytes can become HpSCs in the injured liver.
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Japan. mmasuya@clin.medic.mie-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Masuya
authors.forename: Shiho
authors.initials: S
authors.lastname: Nakamura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yukimoto
authors.forename: Eri
authors.initials: E
authors.lastname: Miyata
authors.forename: Kazuko
authors.initials: K
authors.lastname: Ino
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Kei
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kohshi
authors.initials: K
authors.lastname: Ohishi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D005434:Flow Cytometry; D008099:Liver / Q000166:cytology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse