Reuterdahl C, Sundberg C, Rubin K, Funa K, Gerdin B
Department of Medical and Physiological Chemistry, Biomedical Center, Uppsala, Sweden.
J Clin Invest. 1993 May;91(5):2065-75. doi: 10.1172/JCI116429.
The expression and localization of PDGF beta receptors and PDGF-AB/BB in human healing wounds was evaluated by immunohistochemical techniques and in situ hybridization. Expression of PDGF beta receptor protein and PDGF-AB/BB were analyzed in wound margin biopsies using the PDGFR-B2 and PDGF 007 antibodies. PDGF beta receptor expression was minor in normal skin. An increased expression of PDGF beta receptor protein was prominent in vessels in the proliferating tissue zone in wounds as early as 1 d after surgery and was apparent < or = 4 wk after surgery. There was also a concordant increase in PDGF beta receptor mRNA detected by in situ hybridization. PDGF-AB/BB was present in healing wounds as well as in normal skin. In normal skin, expression of PDGF-AB/BB was confined to peripheral nerve fibers and to solitary cells of the epidermis and of the superficial dermis. In wounds, infiltrating mononuclear cells also stained for PDGF-AB/BB. To identify cell types expressing PDGF AB/BB and PDGF beta receptors, respectively, we performed double immunofluorescence stainings. PDGF beta receptors were expressed by vascular smooth muscle cells and cells in capillary walls; the receptor protein could not be detected in neurofilament containing structures, T lymphocytes, or CD68 expressing macrophages. PDGF-AB/BB colocalized with neurofilaments, it was present in Langerhans cells of the epidermis and in HLA-DR positive cells located in the epidermal/dermal junction area. Of the macrophages infiltrating the wound, 43 +/- 18% stained positively for PDGF AB/BB. Since PDGF-AB/BB and PDGF beta receptors are expressed in the healing wound, two essential prerequisites for a role of PDGF in wound healing are fulfilled.
采用免疫组化技术和原位杂交法评估血小板衍生生长因子β受体(PDGFβ受体)和血小板衍生生长因子AB/BB(PDGF-AB/BB)在人类愈合伤口中的表达及定位。使用PDGFR-B2和PDGF 007抗体分析伤口边缘活检组织中PDGFβ受体蛋白和PDGF-AB/BB的表达。PDGFβ受体在正常皮肤中表达较少。术后1天,伤口增殖组织区血管中PDGFβ受体蛋白表达即显著增加,术后≤4周时仍很明显。原位杂交检测到的PDGFβ受体mRNA也有相应增加。PDGF-AB/BB存在于愈合伤口及正常皮肤中。在正常皮肤中,PDGF-AB/BB的表达局限于外周神经纤维以及表皮和浅表真皮的单个细胞。在伤口中,浸润的单核细胞也可检测到PDGF-AB/BB染色。为分别鉴定表达PDGF AB/BB和PDGFβ受体的细胞类型,我们进行了双重免疫荧光染色。PDGFβ受体由血管平滑肌细胞和毛细血管壁细胞表达;在含有神经丝的结构、T淋巴细胞或表达CD68的巨噬细胞中未检测到该受体蛋白。PDGF-AB/BB与神经丝共定位,存在于表皮的朗格汉斯细胞以及位于表皮/真皮交界区的HLA-DR阳性细胞中。浸润伤口的巨噬细胞中,43±18%对PDGF AB/BB呈阳性染色。由于PDGF-AB/BB和PDGFβ受体在愈合伤口中表达,因此满足了PDGF在伤口愈合中发挥作用的两个基本前提条件。