Utilization of fractionated soluble egg antigens reveals selectively modulated granulomatous and lymphokine responses during murine schistosomiasis mansoni.
Utilization of fractionated soluble egg antigens reveals selectively modulated granulomatous and lymphokine responses during murine schistosomiasis mansoni.
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利用分级可溶性卵抗原揭示了小鼠曼氏血吸虫病期间选择性调节的肉芽肿和淋巴因子反应。
DOI：
10.1128/iai.60.8.3209-3216.1992
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发表时间：
1992
影响因子：
3.1
通讯作者：
Boros,DL
中科院分区：
文献类型：
--
作者：
Lukacs,NW;Boros,DL
在感染曼氏血吸虫的小鼠的肝脏和肠道中沉积的虫卵分泌可溶性虫卵抗原（SEA）并诱导T细胞介导的表皮肉芽肿。本研究采用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳技术对粗SEA进行了分离，并在感染的不同阶段检测了肉芽肿的形成和淋巴因子的产生。采用SEA片段偶联微球诱导人工肺肉芽肿。急性感染小鼠对SEA的7个部分（小于21-、25-至30-、32-至38-、60-至66-、70-至90-、93-至125-和大于200-kDa的部分）有肉芽肿反应，而慢性感染小鼠对4个部分（60-至66-、70-至90-、93-至125-和大于200-kDa的部分）有反应。在对粗SEA和分离SEA的反应中，肉芽肿T细胞在急性前（6周）感染阶段产生高水平的γ干扰素，但随后产生减少。白细胞介素-2 （IL-2）和IL-4的产生在感染急性期（8周）达到高峰，同时在慢性期（20周）下降。在感染的急性期，肉芽肿性SEA组分也诱导了IL-2和IL-4的产生；在慢性阶段，IL-2的产生和较小程度上的IL-4的产生与引起肉芽肿的SEA部分相对应。32- 38-kDa片段分离的SEA蛋白表现出不同的淋巴因子反应：32- kda片段主要诱导γ干扰素和IL-2的产生，而35-和38-kDa片段主要诱导γ干扰素和IL-4的产生。然而，这三种蛋白都能引起肉芽肿的形成。本研究揭示了在感染的急性和慢性阶段肉芽肿对SEA组分的反应的变化，以及在感染的整个过程中γ干扰素、IL-2和IL-4淋巴因子产生的不同阶段。由此可见，肉芽肿的形成与白细胞介素2和白细胞介素4的产生有关。
Worm eggs deposited in the livers and intestines of Schistosoma mansoni-infected mice secrete soluble egg antigens (SEA) and induce T cell-mediated circumoval granulomas. In the present study, we fractionated crude SEA by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tested the fractions for granuloma elicitation and lymphokine production at different stages of the infection. SEA fraction-coupled beads were used to elicit artificial pulmonary granulomas. Acutely infected mice responded with granulomas to seven fractions (less than 21-, 25- to 30-, 32- to 38-, 60- to 66-, 70- to 90-, 93- to 125-, and greater than 200-kDa fractions) of SEA, whereas chronically infected mice responded to four fractions (60- to 66-, 70- to 90-, 93- to 125-, and greater than 200-kDa fractions). In response to both crude and fractionated SEA, granuloma T cells produced high levels of gamma interferon at the preacute (6-week) stage of infection, but production subsequently diminished. Interleukin-2 (IL-2) and IL-4 production peaked at the acute (8-week) stage of infection and concurrently decreased at the chronic (20-week) stage. At the acute stage of the infection, the granulomagenic SEA fractions also elicited IL-2 and IL-4 production; at the chronic stage, IL-2 production and, to a lesser degree, IL-4 production corresponded to SEA fractions that elicited granulomas. Isolated SEA proteins from the 32- to 38-kDa fraction demonstrated differential lymphokine responses: predominant gamma interferon and IL-2 production was elicited by the 32-kDa fraction, whereas the 35- and 38-kDa proteins elicited predominant gamma interferon and IL-4 production. However, all three proteins elicited granuloma formation. The present study reveals changes in granulomatous responses to SEA fractions during the acute and chronic stages of the infection as well as distinct phases of gamma interferon, IL-2, and IL-4 lymphokine production throughout the infection. Based on these results, it is concluded that granuloma formation and IL-2 and IL-4 production are interrelated.