Smith T J, Wang H S, Hogg M G, Henrikson R C, Keese C R, Giaever I
Department of Medicine, Albany Medical College, NY 12208.
Proc Natl Acad Sci U S A. 1994 May 24;91(11):5094-8. doi: 10.1073/pnas.91.11.5094.
Fibroblasts derived from distinct anatomical regions appear to differ in regard to their behavior in culture. These differences may reflect functions of these cells in vivo that are tissue specific. Moreover, intrinsic differences in fibroblasts may underlie the site-specific connective tissue manifestations associated with systemic disease. We have demonstrated previously that orbital fibroblasts exhibit different cytokine response domains and protein synthetic programs when compared to those emanating from the skin. In the present communication, we demonstrate that prostaglandin E2 (PGE2) elicits in cultured human orbital fibroblasts from patients with Graves ophthalmopathy a rapid and dramatic change in cell morphology in vitro as assessed by phase-contrast and scanning electron microscopy. The central areas of the cells become elevated with respect to the plane of the substratum and are stellate, with long processes that touch neighboring cells. These changes occur within 6 hr of prostanoid addition to culture medium at an apparent concentration threshold of approximately 10 nM. Shape changes are accompanied by marked alterations in monolayer impedance as assessed by electric cell-substrate impedance sensing as described previously. Both morphologic and impedance changes elicited by PGE2 revert over 24 hr toward those found in untreated cells despite the continued presence of the prostanoid in the culture medium. In contrast, dermal fibroblasts fail to respond to PGE2. These observations define a previously unrecognized phenotypic attribute of orbital fibroblasts. Intrinsic differences in these cells may account for the anatomic site-selective vulnerability of the orbit in Graves ophthalmopathy. The culture system described here may be useful for studying the morphogenic actions of prostanoids.
源自不同解剖区域的成纤维细胞在培养中的行为似乎有所不同。这些差异可能反映了这些细胞在体内具有组织特异性的功能。此外，成纤维细胞的内在差异可能是与系统性疾病相关的位点特异性结缔组织表现的基础。我们之前已经证明，与皮肤来源的成纤维细胞相比，眼眶成纤维细胞表现出不同的细胞因子反应域和蛋白质合成程序。在本通讯中，我们证明，通过相差显微镜和扫描电子显微镜评估，前列腺素E2（PGE2）在培养的Graves眼病患者的人眼眶成纤维细胞中引发体外细胞形态的快速而显著变化。细胞的中心区域相对于基质平面升高，呈星状，有长突起与相邻细胞接触。这些变化在将前列腺素添加到培养基中6小时内发生，明显的浓度阈值约为10 nM。如前所述，通过电细胞-基质阻抗传感评估，形状变化伴随着单层阻抗的显著改变。尽管培养基中持续存在前列腺素，但PGE2引起的形态和阻抗变化在24小时内恢复到未处理细胞中的状态。相比之下，真皮成纤维细胞对PGE2无反应。这些观察结果定义了眼眶成纤维细胞以前未被认识到的表型特征。这些细胞的内在差异可能解释了Graves眼病中眼眶的解剖位点选择性易损性。这里描述的培养系统可能有助于研究前列腺素的形态发生作用。
