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Wang J, Jiao H, Stewart TL, Shankowsky HA, Scott PG, Tredget EE: Improvement in postburn hypertrophic scar after treatment with IFN-alpha2b is associated with decreased fibrocytes. J Interferon Cytokine Res. 2007 Nov;27(11):921-30.
Hypertrophic scar (HTS) following thermal injury is a dermal fibroproliferative disorder that leads to considerable morbidity. Previous clinical studies from our laboratory have suggested that interferon-alpha2b (IFN-alpha2b) improves scar quality as a result of suppression of fibroblast functions. Fibrocytes, which constitute a unique cell population, have recently been reported to contribute to wound healing and to a variety of fibrotic conditions, including HTS. Therefore, we hypothesize that improvement of scar in HTS patients after IFN-alpha2b treatment may be associated with a decreased number of fibrocytes or altered fibrocyte function. Using flow cytometry, immunofluorescent staining, and confocal microscopy, we demonstrate here that the marker protein leukocyte-specific protein 1 (LSP1) is stably expressed by fibrocytes for at least 2 months, whereas other potential fibrocyte markers, such as CD34 and CD45, gradually disappear. Using dual staining immunohistochemistry for LSP1 and procollagen, we demonstrated a significant reduction in numbers of fibrocytes in HTS tissue from patients after treatment with systemic IFN-alpha2b. IFN-alpha2b was shown to abolish fibrocyte differentiation from peripheral blood mononuclear cells (PBMCs) in vitro in a dose-dependent fashion. In addition, IFN-alpha2b inhibits proliferation of fibrocytes and T lymphocytes and reduces transforming growth factor-beta (TGF-beta)-mediated alpha-smooth muscle actin (alpha-SMA) expression in fibrocytes. Taken together with our previous study in which we showed that fibrocytes could indirectly regulate dermal fibroblasts in burn patients, the present study suggests that the improvement of scar quality in HTS patients after IFN-alpha2b treatment is associated with decreased numbers and activities of fibrocytes. |
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