Molecular Medicine

, Volume 21, Supplement 1, pp S3–S5 | Cite as

Fibrocytes at 20 Years

  • Rick Bucala
Invited Review Article

Since the discovery of the “fibrocyte” as a collagen-producing leukocyte in the 1990s, our knowledge of the physiologic and pathologic role of this unique cell population has grown steadily. Fibrocytes traffic to sites of injury during the earliest phase of the innate immune response and exhibit both the inflammatory features of macrophages and the tissue remodeling properties of fibroblasts. Fibrocytes are distinguished by the simultaneous expression of CD34 or CD45 and collagen. Although these cells were first described in the context of wound repair, accruing evidence supports their central participation in the pathogenesis of different fibrosing disorders. Reliable methods for the enumeration of circulating fibrocytes have been developed, which indicate the utility of such measurements in disease prognosis. Ongoing research is focusing on the molecular signals that influence fibrocyte migration, proliferation and function in the context of normal physiology and pathology....


  1. 1.
    Reilkoff RA, Bucala R, Herzog EL. (2011) Fibrocytes: emerging effector cells in chronic inflammation. Nat. Rev. Immunol. 11:427–35.CrossRefGoogle Scholar
  2. 2.
    Paget J. (1863) Lectures on Surgical Pathology. London: Longmans. pp. 1–848.Google Scholar
  3. 3.
    Chesney J, Metz C, Stavitsky A, Bacher M, Bucala R. (1998) Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes. J. Immunol. 160:419–25.PubMedGoogle Scholar
  4. 4.
    Yang LJ, et al. (2002) Peripheral blood fibrocytes from burn patients: identification and quantification S5 of fibrocytes in adherent cells cultured from peripheral blood mononuclear cells. Lab. Invest. 82:1183–92.CrossRefGoogle Scholar
  5. 5.
    Phillips RJ, et al. (2004) Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J. Clin. Invest. 114:438–46.CrossRefGoogle Scholar
  6. 6.
    Haudek SB, et al. (2006) Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in mice. Proc. Natl. Acad. Sci. U. S. A. 103:18284–9.CrossRefGoogle Scholar
  7. 7.
    Sakai N, et al. (2006) Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis. Proc. Natl. Acad. Sci. U. S. A. 103:14098–103.CrossRefGoogle Scholar
  8. 8.
    Mathai SK, et al. (2010) Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype. Lab. Invest. 90:812–23.CrossRefGoogle Scholar
  9. 9.
    Cowper SE, Bucala R. (2003) Nephrogenic fibrosing dermopathy: suspect identified, motive unclear. Am. J. Dermatopathol. 25:358–8.CrossRefGoogle Scholar
  10. 10.
    Galligan CL, Fish EN. (2012) Circulating fibrocytes contribute to the pathogenesis of arthritis. Arthritis Rheum. 64:3583–93.CrossRefGoogle Scholar
  11. 11.
    Douglas RS, et al. (2010) Increased generation of fibrocytes in thyroid-associated ophthalmopathy. J. Clin. Endocrinol. Metab. 95:430–8.CrossRefGoogle Scholar
  12. 12.
    Chesney J, Bacher M, Bender A, Bucala R. (1997) The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T-cells in situ. Proc. Natl. Acad. Sci. U. S. A. 94:6307–12.CrossRefGoogle Scholar
  13. 13.
    Mehrad B, et al. (2007) Circulating peripheral blood fibrocytes in human fibrotic interstitial lung disease. Biochem. Biophys. Res. Comm. 353:104–8.CrossRefGoogle Scholar
  14. 14.
    Schmidt M, Sun G, Stacey MA, Mori L, Mattoli S. (2003) Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma. J. Immunol. 171:380–9.CrossRefGoogle Scholar
  15. 15.
    Moeller A, et al. (2009) Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 179:588–94.CrossRefGoogle Scholar
  16. 16.
    Pilling D, Zheng Z, Vakil V, Gomer RH. (2014) Fibroblasts secrete Slit2 to inhibit fibrocyte differentiation and fibrosis. Proc. Natl. Acad. Sci. U. S. A. 111:18291–6.CrossRefGoogle Scholar
  17. 17.
    Pilling D, Buckley CD, Salmon M, Gomer RH. (2003) Inhibition of fibrocyte differentiation by serum amyloid P. J. Immunol. 171:5537–46.CrossRefGoogle Scholar
  18. 18.
    Niedermeier M, et al. (2009) CD4(+) T cells control the differentiation of Gr1(+) monocytes into fibrocytes. Proc. Natl. Acad. Sci. U. S. A. 106:17892–7.CrossRefGoogle Scholar
  19. 19.
    Lupher ML Jr. (2012) Recombinant Human Pentraxin-2 (PRM-151): Leveraging Nature’s Mechanism of Fibrocyte and Monocyte Regulation to Treat Disease. In: Fibrocytes in Health and Disease. Bucala R [ed.] World Scientific, Hackensack, NJ, pp. 285–314.Google Scholar
  20. 20.
    Pilling D, Tucker NM, Gomer RH. (2006) Aggregated IgG inhibits the differentiation of human fibrocytes. J. Leukocyte Biol. 79:1242–1251.CrossRefGoogle Scholar

Copyright information

© The Author(s) 2014

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it.

The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this license, visit (

Authors and Affiliations

  • Rick Bucala
    • 1
    • 2
    • 3
  1. 1.Department of MedicineYale University School of MedicineNew HavenUSA
  2. 2.Department of PathologyYale University School of MedicineNew HavenUSA
  3. 3.Department of Epidemiology & Public HealthYale University School of MedicineNew HavenUSA

Personalised recommendations