Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Region Metropolitana, Santiago de Chile 8380453, Chile.
Placenta. 2012 Dec;33(12):991-7. doi: 10.1016/j.placenta.2012.10.004. Epub 2012 Oct 26.
Chagas' disease is caused by the haemophlagelated protozoan Trypanosoma cruzi (T. cruzi). During congenital transmission the parasite breaks down the placental barrier. In the present study we analyzed the participation of matrix metalloproteases (MMPs) in the extracellular matrix (ECM) remodeling during T. cruzi ex vivo infection of human placental chorionic villi explants.
Chorionic villi from healthy woman placentas were incubated in the presence or absence of 10⁵ or 10⁶ T. cruzi trypomastigotes (Y strain) with or without the MMPs inhibitor doxycycline. Effective infection was tested measuring parasite DNA by real time PCR (qPCR). MMP-2 and MMP-9 expression were determined by western blotting and immunohistochemistry and their activities were measured by zymography. The effect of MMPs on ECM structure was analyzed histochemically.
T. cruzi induces the expression and activity of MMP-2 and MMP-9 in chorionic villi. Inhibition of the MMPs prevents the tissue damage induced by T. cruzi and partially decreases the ex vivo infection of the chorionic villi.
MMPs are partially responsible for the ECM changes observed in human chorionic villi during T. cruzi infection and participate in tissue invasion. On the other hand, MMPs may be part of a local placental antiparasitic mechanism.
恰加斯病是由血鞭毛原生动物克氏锥虫（T. cruzi）引起的。在先天性传播过程中，寄生虫会破坏胎盘屏障。在本研究中，我们分析了基质金属蛋白酶（MMPs）在克氏锥虫体外感染人胎盘绒毛外植体的细胞外基质（ECM）重塑过程中的参与情况。
用或不用 MMPs 抑制剂强力霉素（doxycycline），在存在或不存在 10⁵或 10⁶个 T. cruzi 动基体（Y 株）的情况下，孵育来自健康女性胎盘的绒毛。通过实时 PCR（qPCR）测量寄生虫 DNA 来检测有效的感染。通过 Western blot 和免疫组织化学测定 MMP-2 和 MMP-9 的表达，并通过酶谱法测定其活性。通过组织化学分析 MMPs 对 ECM 结构的影响。
T. cruzi 在绒毛中诱导 MMP-2 和 MMP-9 的表达和活性。MMPs 的抑制可防止 T. cruzi 引起的组织损伤，并部分降低绒毛的体外感染。
MMPs 部分负责 T. cruzi 感染期间人绒毛中 ECM 变化，并参与组织侵袭。另一方面，MMPs 可能是胎盘局部抗寄生虫机制的一部分。
