Fibrocytes are involved in inflammation as well as fibrosis in the pathogenesis of Crohn's disease

Dig Dis Sci. 2014 Apr;59(4):760-8. doi: 10.1007/s10620-013-2813-8. Epub 2013 Aug 22.

Abstract

Background: We previously showed that fibrocytes, a hematopoietic stem cell source of fibroblasts/myofibroblasts, infiltrated the colonic mucosa of a murine colitis model.

Aim: 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.

MeSH terms

  • Cells, Cultured
  • Collagen Type I / physiology
  • Crohn Disease / etiology
  • Crohn Disease / metabolism
  • Crohn Disease / pathology*
  • Crohn Disease / physiopathology*
  • Fibroblasts / metabolism
  • Fibroblasts / physiology*
  • Fibrosis
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism
  • Receptors, CXCR4 / physiology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Collagen Type I
  • Receptors, CXCR4
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1