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. 1994 Nov;1(1):71–81.

Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair.

R Bucala 1, L A Spiegel 1, J Chesney 1, M Hogan 1, A Cerami 1
PMCID: PMC2229929  PMID: 8790603

Abstract

BACKGROUND: The host response to tissue injury requires a complex interplay of diverse cellular, humoral, and connective tissue elements. Fibroblasts participate in this process by proliferating within injured sites and contributing to scar formation and the longterm remodeling of damaged tissue. Fibroblasts present in areas of tissue injury generally have been regarded to arise by recruitment from surrounding connective tissue; however this may not be the only source of these cells. MATERIALS AND METHODS: Long-term culture of adherent, human, and murine leukocyte subpopulations was combined with a variety of immunofluorescence and functional analyses to identify a blood-borne cell type with fibroblast-like properties. RESULTS: We describe for the first time a population of circulating cells with fibroblast properties that specifically enter sites of tissue injury. This novel cell type, termed a "fibrocyte," was characterized by its distinctive phenotype (collagen+/vimentin+/CD34+), by its rapid entry from blood into subcutaneously implanted wound chambers, and by its presence in connective tissue scars. CONCLUSIONS: Blood-borne fibrocytes contribute to scar formation and may play an important role both in normal wound repair and in pathological fibrotic responses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews R. G., Singer J. W., Bernstein I. D. Monoclonal antibody 12-8 recognizes a 115-kd molecule present on both unipotent and multipotent hematopoietic colony-forming cells and their precursors. Blood. 1986 Mar;67(3):842–845. [PubMed] [Google Scholar]
  2. Berenson R. J., Andrews R. G., Bensinger W. I., Kalamasz D., Knitter G., Buckner C. D., Bernstein I. D. Antigen CD34+ marrow cells engraft lethally irradiated baboons. J Clin Invest. 1988 Mar;81(3):951–955. doi: 10.1172/JCI113409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brecher G., Lawce H., Tjio J. H. Bone marrow transfusions in previously irradiated, hematologically normal syngeneic mice. Proc Soc Exp Biol Med. 1981 Mar;166(3):389–393. doi: 10.3181/00379727-166-41079. [DOI] [PubMed] [Google Scholar]
  4. Brown J., Greaves M. F., Molgaard H. V. The gene encoding the stem cell antigen, CD34, is conserved in mouse and expressed in haemopoietic progenitor cell lines, brain, and embryonic fibroblasts. Int Immunol. 1991 Feb;3(2):175–184. doi: 10.1093/intimm/3.2.175. [DOI] [PubMed] [Google Scholar]
  5. Bucala R., Ritchlin C., Winchester R., Cerami A. Constitutive production of inflammatory and mitogenic cytokines by rheumatoid synovial fibroblasts. J Exp Med. 1991 Mar 1;173(3):569–574. doi: 10.1084/jem.173.3.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Civin C. I., Strauss L. C., Brovall C., Fackler M. J., Schwartz J. F., Shaper J. H. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol. 1984 Jul;133(1):157–165. [PubMed] [Google Scholar]
  7. Diegelmann R. F., Lindblad W. J., Cohen I. K. A subcutaneous implant for wound healing studies in humans. J Surg Res. 1986 Mar;40(3):229–237. doi: 10.1016/0022-4804(86)90156-3. [DOI] [PubMed] [Google Scholar]
  8. Fahey T. J., 3rd, Sherry B., Tracey K. J., van Deventer S., Jones W. G., 2nd, Minei J. P., Morgello S., Shires G. T., Cerami A. Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1. Cytokine. 1990 Mar;2(2):92–99. doi: 10.1016/1043-4666(90)90002-b. [DOI] [PubMed] [Google Scholar]
  9. Fina L., Molgaard H. V., Robertson D., Bradley N. J., Monaghan P., Delia D., Sutherland D. R., Baker M. A., Greaves M. F. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990 Jun 15;75(12):2417–2426. [PubMed] [Google Scholar]
  10. Franke W. W., Schmid E., Winter S., Osborn M., Weber K. Widespread occurrence of intermediate-sized filaments of the vimentin-type in cultured cells from diverse vertebrates. Exp Cell Res. 1979 Oct 1;123(1):25–46. doi: 10.1016/0014-4827(79)90418-x. [DOI] [PubMed] [Google Scholar]
  11. Golde D. W., Hocking W. G., Quan S. G., Sparkes R. S., Gale R. P. Origin of human bone marrow fibroblasts. Br J Haematol. 1980 Feb;44(2):183–187. doi: 10.1111/j.1365-2141.1980.tb01200.x. [DOI] [PubMed] [Google Scholar]
  12. Katz F. E., Tindle R., Sutherland D. R., Greaves M. F. Identification of a membrane glycoprotein associated with haemopoietic progenitor cells. Leuk Res. 1985;9(2):191–198. doi: 10.1016/0145-2126(85)90082-7. [DOI] [PubMed] [Google Scholar]
  13. Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
  14. Sinclair A. H., Berta P., Palmer M. S., Hawkins J. R., Griffiths B. L., Smith M. J., Foster J. W., Frischauf A. M., Lovell-Badge R., Goodfellow P. N. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 1990 Jul 19;346(6281):240–244. doi: 10.1038/346240a0. [DOI] [PubMed] [Google Scholar]
  15. Torry D. J., Richards C. D., Podor T. J., Gauldie J. Anchorage-independent colony growth of pulmonary fibroblasts derived from fibrotic human lung tissue. J Clin Invest. 1994 Apr;93(4):1525–1532. doi: 10.1172/JCI117131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Virtanen I., Lehto V. P., Lehtonen E., Vartio T., Stenman S., Kurki P., Wager O., Small J. V., Dahl D., Badley R. A. Expression of intermediate filaments in cultured cells. J Cell Sci. 1981 Aug;50:45–63. doi: 10.1242/jcs.50.1.45. [DOI] [PubMed] [Google Scholar]

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