Selam Belgin, Kayisli Umit A, Garcia-Velasco Juan A, Arici Aydin
Yale University School of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, New Haven, Connecticut 06520, USA.
Biol Reprod. 2002 Jan;66(1):1-5. doi: 10.1095/biolreprod66.1.1.
Interaction between endometrial stromal cells and extracellular matrix (ECM) components has a crucial role in the development of endometriosis. Endometrial stromal cells attach to the mesothelial surface of peritoneum by means of integrins during their initial implantation and growth in endometriosis. Similarly, interaction between integrin and the extracellular matrix is also crucial for the remodeling of the endometrium during early pregnancy. We hypothesized that adhesion of endometrial stromal cells to the extracellular matrix could suppress the immunologic reaction to implanting endometrial cells by inducing the expression of Fas ligand (FasL), a mediator of the apoptotic pathway. Western blot analysis of human endometrial stromal cells plated onto fibronectin, laminin, and collagen IV revealed higher levels of FasL protein expression compared with endometrial stromal cells that plated to BSA-coated plates (control). Immunocytochemistry results from endometrial stromal cells plated to extracellular matrix proteins demonstrated a similar up-regulation of FasL expression. Eutopic endometrial stromal cells from women with endometriosis demonstrated higher FasL expression on control plates and those coated with extracellular matrix proteins compared with those from women without endometriosis. Disruption of actin cytoskeleton in endometrial stromal cells by treatment with cytochalasin D blocked the increase of FasL protein expression that occurred in response to adhesion to the extracellular matrix. These results suggest that attachment of endometrial stromal cells during retrograde menstruation to a new environment such as peritoneum with increased expression of laminin, fibronectin, and collagen IV could lead to an increase in FasL expression. Induction of FasL expression by adhesion of endometrial stromal cells to the extracellular matrix may take part in the development of a relative immunotolerance by inducing apoptosis of cytotoxic T lymphocytes, which will allow further development of ectopic implants.
子宫内膜基质细胞与细胞外基质（ECM）成分之间的相互作用在子宫内膜异位症的发展中起着关键作用。在子宫内膜异位症的初始植入和生长过程中，子宫内膜基质细胞通过整合素附着于腹膜的间皮表面。同样，整合素与细胞外基质之间的相互作用对于早期妊娠期间子宫内膜的重塑也至关重要。我们推测，子宫内膜基质细胞与细胞外基质的黏附可通过诱导凋亡途径的介质Fas配体（FasL）的表达来抑制对植入子宫内膜细胞的免疫反应。对接种于纤连蛋白、层粘连蛋白和IV型胶原上的人子宫内膜基质细胞进行的蛋白质免疫印迹分析显示，与接种于牛血清白蛋白包被平板（对照）上的子宫内膜基质细胞相比，FasL蛋白表达水平更高。接种于细胞外基质蛋白上的子宫内膜基质细胞的免疫细胞化学结果显示FasL表达有类似的上调。与无子宫内膜异位症女性的异位子宫内膜基质细胞相比，有子宫内膜异位症女性的在位子宫内膜基质细胞在对照平板和包被有细胞外基质蛋白的平板上表现出更高的FasL表达。用细胞松弛素D处理破坏子宫内膜基质细胞中的肌动蛋白细胞骨架，可阻断因与细胞外基质黏附而发生的FasL蛋白表达增加。这些结果表明，逆行月经期间子宫内膜基质细胞附着于新环境（如层粘连蛋白、纤连蛋白和IV型胶原表达增加的腹膜）可能导致FasL表达增加。子宫内膜基质细胞与细胞外基质黏附诱导FasL表达可能通过诱导细胞毒性T淋巴细胞凋亡参与相对免疫耐受的形成，从而使异位植入物得以进一步发展。
