Soeiro M de N, Paiva M M, Waghabi M C, Meirelles M de N, Lorent K, Henriques-Pons A, Coutinho C M, Van Leuven F, Araújo-Jorge T C
Lab. Biologia Celular, DUBC, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Exp Parasitol. 2000 Oct;96(2):97-107. doi: 10.1006/expr.2000.4555.
Although a complete cellular and humoral immune response is elicited in Chagas' disease, recent data suggest that other natural elements of innate immunity may also contribute to the initial host primary defense. alpha-Macroglobulins are a family of plasma proteinase inhibitors that are acute-phase reactants in Trypanosoma cruzi-infected mice and humans. Mice contain a tetrameric alpha-2-macroglobulin (MAM) and a monomeric murinoglobulin (MUG). Heterogeneity in their reactions was observed in murine T. cruzi-infected plasma A2M levels despite an overall increase. In addition, up-regulation of the A2M receptor (A2MR/LRP) was observed in peritoneal macrophages during T. cruzi infection. Here, we show that during T. cruzi infection (Y strain), the MAM and MUG hepatic mRNA levels and the corresponding plasma protein levels were up-regulated in C3H and C57BL/6 (B6) mice, but with different kinetics. On the contrary, A2MR/LRP mRNA levels increased in acutely infected C3H mice, but decreased in B6 mice, in both liver and heart. Immunocytochemistry of infected B6 heart cryosections confirmed a less intense endothelium labeling by the fluoresceinated ligand for A2MR/LRP. On the other hand, infected B6 spleen cells displayed higher F-A2M-FITC binding and MAC1 expression, confirming higher A2MR/LRP expression in macrophages. In uninfected mice, as well as after T. cruzi infection, higher A2M plasma levels were measured in C3H mice than in B6 mice. The lower tissue T. cruzi parasitism found in C3H-infected mice could reflect an inhibitory effect of A2M on parasite invasion. Our present data further contribute to clarifying aspects of the role of A2MR/LRP in a model of acute Chagas' disease in different mouse strains.
尽管恰加斯病会引发完整的细胞免疫和体液免疫反应，但最近的数据表明，先天免疫的其他天然成分也可能有助于宿主的初始主要防御。α-巨球蛋白是一类血浆蛋白酶抑制剂，是克氏锥虫感染小鼠和人类时的急性期反应物。小鼠含有一种四聚体α-2-巨球蛋白（MAM）和一种单体鼠球蛋白（MUG）。尽管总体上有所增加，但在感染克氏锥虫的小鼠血浆A2M水平中观察到了它们反应的异质性。此外，在克氏锥虫感染期间，腹膜巨噬细胞中A2M受体（A2MR/LRP）上调。在此，我们表明，在克氏锥虫（Y株）感染期间，C3H和C57BL/6（B6）小鼠的MAM和MUG肝脏mRNA水平以及相应的血浆蛋白水平上调，但动力学不同。相反，急性感染的C3H小鼠肝脏和心脏中的A2MR/LRP mRNA水平增加，而B6小鼠中则降低。感染的B6心脏冰冻切片的免疫细胞化学证实，用于A2MR/LRP的荧光配体对内皮的标记较弱。另一方面，感染的B6脾细胞显示出更高的F-A2M-FITC结合和MAC1表达，证实巨噬细胞中A2MR/LRP表达更高。在未感染的小鼠以及克氏锥虫感染后，C3H小鼠的血浆A2M水平高于B6小鼠。在C3H感染的小鼠中发现较低的组织克氏锥虫寄生可能反映了A2M对寄生虫入侵的抑制作用。我们目前的数据进一步有助于阐明A2MR/LRP在不同小鼠品系急性恰加斯病模型中的作用。
