title: Identification of markers that distinguish monocyte-derived fibrocytes from monocytes, macrophages, and fibroblasts.
abstract: BACKGROUND
  The processes that drive fibrotic diseases are complex and include an influx of peripheral blood monocytes that can differentiate into fibroblast-like cells called fibrocytes. Monocytes can also differentiate into other cell types, such as tissue macrophages. The ability to discriminate between monocytes, macrophages, fibrocytes, and fibroblasts in fibrotic lesions could be beneficial in identifying therapies that target either stromal fibroblasts or fibrocytes.
  
  
  RESULTS
  We have identified markers that discriminate between human peripheral blood monocytes, tissue macrophages, fibrocytes, and fibroblasts. Amongst these four cell types, only peripheral blood monocytes express the combination of CD45RO, CD93, and S100A8/A9; only macrophages express the combination of CD45RO, 25F9, S100A8/A9, and PM-2K; only fibrocytes express the combination of CD45RO, 25F9, and S100A8/A9, but not PM-2K; and only fibroblasts express the combination of CD90, cellular fibronectin, hyaluronan, and TE-7. These markers are effective both in vitro and in sections from human lung. We found that markers such as CD34, CD68, and collagen do not effectively discriminate between the four cell types. In addition, IL-4, IL-12, IL-13, IFN-gamma, and SAP differentially regulate the expression of CD32, CD163, CD172a, and CD206 on both macrophages and fibrocytes. Finally, CD49c (alpha3 integrin) expression identifies a subset of fibrocytes, and this subset increases with time in culture.
  
  
  CONCLUSIONS
  These results suggest that discrimination of monocytes, macrophages, fibrocytes, and fibroblasts in fibrotic lesions is possible, and this may allow for an assessment of fibrocytes in fibrotic diseases.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States of America. dpilling@rice.edu
authors.forename: Darrell
authors.initials: D
authors.lastname: Pilling
authors.forename: Ted
authors.initials: T
authors.lastname: Fan
authors.forename: Donna
authors.initials: D
authors.lastname: Huang
authors.forename: Bhavika
authors.initials: B
authors.lastname: Kaul
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gomer
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001769:Blood / Q000378:metabolism; D040501:Calgranulin A / Q000096:biosynthesis; D040502:Calgranulin B / Q000096:biosynthesis; D002469:Cell Separation / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology*; D011951:Receptors, Complement / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D017493:Leukocyte Common Antigens