title: Fibrocytes are involved in inflammation as well as fibrosis in the pathogenesis of Crohn's disease.
abstract: BACKGROUND
  We previously showed that fibrocytes, a hematopoietic stem cell source of fibroblasts/myofibroblasts, infiltrated the colonic mucosa of a murine colitis model.
  
  
  OBJECTIVE
  We investigated whether fibrocytes were involved in the pathogenesis of Crohn's disease.
  
  
  METHODS
  Human surgical intestinal specimens were stained with anti-leukocyte-specific protein 1 and anti-collagen type-I (ColI) antibodies. Circulating fibrocytes in the human peripheral blood were quantified by fluorescence-activated cell sorting with anti-CD45 and anti-ColI antibodies. Cultured human fibrocytes were prepared by culturing peripheral CD14(+) monocytes.
  
  
  RESULTS
  In the specimens of patients with Crohn's disease, the fibrocyte/total leukocyte percentage was significantly increased in inflammatory lesions (22.2 %, p < 0.01) compared with that in non-affected areas of the intestine (2.5 %). Interestingly, the percentage in fibrotic lesions was similar (2.2 %, p = 0.87) to that in non-affected areas. The percentages of circulating fibrocytes/total leukocytes were significantly higher in patients with Crohn's disease than in healthy controls. Both CXC-chemokine receptor 4(+) and intercellular adhesion molecule 1(+) fibrocyte numbers were significantly increased in Crohn's disease, suggesting that circulating fibrocytes have a higher ability to infiltrate injured sites and traffic leukocytes. In cultured fibrocytes, lipopolysaccharide treatment remarkably upregulated tumor necrosis factor (TNF)-α mRNA (17.0 ± 5.7-fold) and ColI mRNA expression (12.8 ± 5.7-fold), indicating that fibrocytes stimulated by bacterial components directly augmented inflammation as well as fibrosis.
  
  
  CONCLUSIONS
  Fibrocytes are recruited early in the inflammatory phase and likely differentiate into fibroblasts/myofibroblasts until the fibrosis phase. They may enhance inflammation by producing TNF-α and can directly augment fibrosis by producing ColI.
authors: Department of Gastroenterology and Nephrology (K1), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, 260-8670, Japan.
authors: Sayuri
authors: S
authors: Sazuka
authors: Tatsuro
authors: T
authors: Katsuno
authors: Tomoo
authors: T
authors: Nakagawa
authors: Masaya
authors: M
authors: Saito
authors: Keiko
authors: K
authors: Saito
authors: Daisuke
authors: D
authors: Maruoka
authors: Tomoaki
authors: T
authors: Matsumura
authors: Makoto
authors: M
authors: Arai
authors: Hideaki
authors: H
authors: Miyauchi
authors: Hisahiro
authors: H
authors: Matsubara
authors: Osamu
authors: O
authors: Yokosuka
mesh_terms: D002478:Cells, Cultured; D024042:Collagen Type I / Q000502:physiology; D003424:Crohn Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D005355:Fibrosis; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1
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