Abstract
BackgroundThe 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.Methodology/Principal FindingsWe 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-γ, and SAP differentially regulate the expression of CD32, CD163, CD172a, and CD206 on both macrophages and fibrocytes. Finally, CD49c (α3 integrin) expression identifies a subset of fibrocytes, and this subset increases with time in culture.Conclusions/SignificanceThese 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.
Highlights
There are multiple sources of fibroblast-like cells present in fibrotic lesions and healing wounds [1,2,3,4,5]
Conclusions/Significance: 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
We found that we can exploit the expression of PM-2K on macrophages and the lack of PM-2K expression on fibrocytes to distinguish fibrocytes from macrophages in human in vitro cultured cells and human lung tissue
Summary
There are multiple sources of fibroblast-like cells present in fibrotic lesions and healing wounds [1,2,3,4,5]. In addition to the proliferation of resident fibroblasts, bone marrow-derived hematopoietic precursors present within the blood are attracted to sites of injury where they differentiate into spindle-shaped fibroblastlike cells called fibrocytes, and at least in part, mediate tissue repair and fibrosis [6,7,8,9,10,11,12,13,14]. Mature fibrocytes exposed to TGF-b in vitro are able to develop further into myofibrocytes, a myofibroblast-like population of cells that express a-SMA and are able to contract collagen gels, in an in vitro model of wound contraction [7]. 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. 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
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