Kołodziej-Sobocińska Marta
Praca doktorska wykonana w Instytucie Parazytologii im. Witolda Stefańskiego PAN w Warszawie i obroniona 20 czerwca 2006 r.
Wiad Parazytol. 2006;52(3):239-41.
The aim of the study was to examine the influence of free radicals: nitric oxide (NO), hydrogen peroxide (H202) and superoxide anion (O2-) on Trichinella spiralis infection in mice. The studies were performed on two strains of mice: C57BL/6 and BALB/c, which differ in immunological response to T. spiralis infection. Also the influence of AG--inhibitor of inducible nitric oxide synthase (iNOS) administered in the first days after T. spiralis infection (1-5 dpi) on the cytotoxic immune response and on the number of adult parasites as well as the influence of AG administered at the beginning of muscle phase of the T. spiralis infection (16-29 dpi) on the cytotoxic immune response and the number of muscle larvae was studied. Activation of macrophages can cause pathology. Contact of macrophages with antigens stimulates these cells to produce, among others, highly reactive inorganic compounds. There are free radicals: NO, H2O2 and O2-. NO, O2-, and their metabolites are highly toxic for most pathogens, including parasites. However, little is known about their role in the defense against T. spiralis infection. The performed studies have proved, that free radicals play role in the host immune response during both intestinal and muscle phase of T. spiralis infection in mice. In the intestinal phase of the T. spiralis infection cytotoxic immune response is activated in mice peritoneal cavity and in the muscle phase, the local immune response activated in the neighborhood of larvae in muscles appeared as the higher level of free radicals in blood and urine. Administration of AG between 1-5 dpi causes opposite reactions in two different strains of mice. In BALB/c mice AG causes fast expulsion of adult T. spiralis from the intestine but in C57BL/6 mice the expulsion of parasites is slower after AG. However, there are no differences between two strains of mice after treatment with AG between 16 and 29 dpi. AG causes diminution of larvae in muscles of both BALB/c and C57BL/6 mice. Inflammatory response in peritoneal cavity is observed later during the infection in "low responders" (C57BL/6) mice in comparison with "high responders" (BALB/c) mice. Thl like mice (C57BL/6) react stronger to AG treatment than Th2 like mice (BALB/c). It occurs as changes and fluctuations in free radicals levels and the number of peritoneal cells after AG treatment in C57BL/6 mice. Weak or no reaction on AG injections in BALB/c mice is responsible for more stabile and more sufficient defense response of the host to T. spiralis infection.
一氧化氮(NO)、过氧化氢(H2O2)和超氧阴离子(O2-)对小鼠旋毛虫感染的影响。研究在两种小鼠品系上进行:C57BL/6和BALB/c,它们对旋毛虫感染的免疫反应不同。同时还研究了在旋毛虫感染后第1天至第5天(感染后1 - 5天)给予诱导型一氧化氮合酶(iNOS)的AG抑制剂对细胞毒性免疫反应和成虫寄生虫数量的影响,以及在旋毛虫感染肌肉期开始时(感染后16 - 29天)给予AG对细胞毒性免疫反应和肌肉幼虫数量的影响。巨噬细胞的激活可导致病理变化。巨噬细胞与抗原接触会刺激这些细胞产生,其中包括高反应性无机化合物。存在自由基:NO、H2O2和O2-。NO、O2-及其代谢产物对大多数病原体,包括寄生虫,具有高毒性。然而,它们在抵御旋毛虫感染中的作用却鲜为人知。所进行的研究证明,自由基在小鼠旋毛虫感染的肠道期和肌肉期的宿主免疫反应中均发挥作用。在旋毛虫感染的肠道期,小鼠腹腔内的细胞毒性免疫反应被激活,而在肌肉期,肌肉中幼虫附近激活的局部免疫反应表现为血液和尿液中自由基水平升高。在感染后1 - 5天给予AG在两种不同品系的小鼠中会引起相反的反应。在BALB/c小鼠中,AG可使成虫旋毛虫快速从肠道排出,但在C57BL/6小鼠中,给予AG后寄生虫的排出较慢。然而,在感染后16至29天用AG处理后,两种小鼠品系之间没有差异。AG可使BALB/c和C57BL/6小鼠肌肉中的幼虫数量减少。与“高反应者”(BALB/c)小鼠相比,“低反应者”(C57BL/6)小鼠在感染后期观察到腹腔内的炎症反应。Th1样小鼠(C57BL/6)对AG处理的反应比Th2样小鼠(BALB/c)更强。这表现为C57BL/6小鼠在AG处理后自由基水平和腹腔细胞数量的变化和波动。BALB/c小鼠对AG注射的反应较弱或无反应,这导致宿主对旋毛虫感染的防御反应更稳定、更充分。