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Digestive Diseases and Sciences

, Volume 59, Issue 4, pp 760–768 | Cite as

Fibrocytes Are Involved in Inflammation as well as Fibrosis in the Pathogenesis of Crohn’s Disease

  • Sayuri Sazuka
  • Tatsuro KatsunoEmail author
  • Tomoo Nakagawa
  • Masaya Saito
  • Keiko Saito
  • Daisuke Maruoka
  • Tomoaki Matsumura
  • Makoto Arai
  • Hideaki Miyauchi
  • Hisahiro Matsubara
  • Osamu Yokosuka
Original Article

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.

Keywords

Collagen type-I (ColI) CXC-chemokine receptor 4 (CXCR4) Intercellular adhesion molecule 1 (ICAM1) Leukocyte-specific protein 1 (LSP-1) Lipopolysaccharide (LPS) 

Notes

Acknowledgments

We are grateful to Yoshiko Noguchi and Fumie Saegusa for excellent technical assistance.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sayuri Sazuka
    • 1
  • Tatsuro Katsuno
    • 1
    Email author
  • Tomoo Nakagawa
    • 1
  • Masaya Saito
    • 1
  • Keiko Saito
    • 1
  • Daisuke Maruoka
    • 1
  • Tomoaki Matsumura
    • 1
  • Makoto Arai
    • 1
  • Hideaki Miyauchi
    • 2
  • Hisahiro Matsubara
    • 2
  • Osamu Yokosuka
    • 1
  1. 1.Department of Gastroenterology and Nephrology (K1), Graduate School of MedicineChiba UniversityChuo-kuJapan
  2. 2.Department of Frontier Surgery (M9), Graduate School of MedicineChiba UniversityChibaJapan

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