Fibronectin and α5 integrin regulate keratinocyte cell cycling -: A mechanism for increased fibronectin potentiation of T cell lymphokine-driven keratinocyte hyperproliferation in psoriasis
Fibronectin and α5 integrin regulate keratinocyte cell cycling -: A mechanism for increased fibronectin potentiation of T cell lymphokine-driven keratinocyte hyperproliferation in psoriasis
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DOI：
10.1172/jci171
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发表时间：
1998-04-01
影响因子：
15.9
通讯作者：
Hammerberg, C
中科院分区：
文献类型：
--
作者：
Bata-Csorgo, Z;Cooper, KD;Hammerberg, C
除了T淋巴细胞驱动外，银屑病的部分原因可能是整合素的异常表达。对银屑病患者外观正常(未受累)的皮肤进行检查，以确定在银屑病皮损发展之前是否可以检测到纤维连接蛋白或其受体的表达改变。与正常人皮肤相比，我们用免疫荧光法检测到银屑病非皮损皮肤表皮基底细胞层中血浆纤维连接蛋白的异常存在。此外，纤维连接蛋白暴露的增加在体外超诱导细胞周期诱导和银屑病非皮损角质形成细胞的扩张，以响应T细胞淋巴因子的鸡尾酒。纤维连接蛋白单独似乎也增加了未受累但不是正常角质形成细胞的细胞周期。与之一致的是，α5整合素纤维连接蛋白受体在活体非皮损银屑病表皮中过度表达，而不是α2或α3。通过抗α5单抗对纤维连接蛋白上角质形成细胞生长的抑制作用，证实了α5β1参与了体外培养的克隆性角质形成细胞的早期生长。因此，纤维连接蛋白受体似乎是银屑病角质形成细胞对银屑病皮损内T淋巴细胞产生的淋巴因子所提供的增殖信号的高反应性所必需的成分之一。
In addition to being T lymphocyte-driven, psoriasis may be due in part to abnormal integrin expression. Normal-appearing (uninvolved) skin from psoriatic patients was examined to determine whether altered fibronectin or its receptor expression is detectable before development of psoriatic lesions. In contrast to skin from normal subjects, we detect by immunofluorescence the abnormal presence of plasma fibronectin in the basal cell layer of the epidermis of psoriatic uninvolved skin. Furthermore, increased fibronectin exposure superinduces the in vitro cell cycle induction and expansion of psoriatic nonlesional keratinocytes in response to a cocktail of T cell lymphokines. Fibronectin alone also appeared to increase cell cycle entry among uninvolved but not normal keratinocytes. Concordantly, the alpha 5 integrin fibronectin receptor, but not alpha 2 or alpha 3, is overexpressed in the in vivo nonlesional psoriatic epidermis. The involvement of alpha 5 beta 1 in the early outgrowth of clonogenic keratinocytes in the ex vivo culture was demonstrated by the ability of anti-alpha 5 mAb to inhibit keratinocyte growth on fibronectin. Thus, the fibronectin receptor appears to be one of the components required for the development of the hyperresponsiveness of psoriatic keratinocytes to signals for proliferation provided by lymphokines produced by intralesional T lymphocytes in psoriasis.