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砷化镓选择性抑制T细胞增殖并改变CD25(白细胞介素-2受体/p55)的表达。

Gallium arsenide selectively inhibits T cell proliferation and alters expression of CD25 (IL-2R/p55).

作者信息

Burns L A, Munson A E

机构信息

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.

出版信息

J Pharmacol Exp Ther. 1993 Apr;265(1):178-86.

PMID:8097242
Abstract

Exposure (24 hr) to a single intratracheal administration of gallium arsenide (GaAs; 200 mg/kg) has been shown to suppress antibody production as well as other T cell-mediated immunological functions. GaAs has also been shown to exert toxic effects on events occurring early in the antibody-forming cell response which may include lymphocyte activation and proliferation. Studies were undertaken to determine whether GaAs exposure resulted in the inability of T and B lymphocytes to proliferate in response to an antigenic stimulus. During the first 24 hr after in vitro immunization with sheep red blood cells, GaAs-exposed splenocytes were suppressed 51% in their ability to proliferate compared to the vehicle (0.05% Tween 80 in saline; VH) control. There was no significant difference in absolute numbers of cluster designation (CD)8+ cells between VH- and GaAs-exposed cultures. There was, however, a 50% decrease in CD4+ cells evaluated 24 hr after immunization with sheep red blood cells which persisted for the 5-day culture period. T and B cells were isolated and analyzed for proliferative capacity in response to various mitogenic stimuli. Isolated B cells exhibited no difference between VH- and GaAs-exposed cells in proliferative capacity to either lipopolysaccharide or anti-immunoglobulin plus interleukin-4. However, isolated T cells exposed to GaAs were significantly suppressed in their ability to proliferate to concanavalin A, phytohemagglutinin and anti-CD3 epsilon plus interleukin-2 when compared to VH. In addition, expression of CD25, leukocyte function antigen-1 and intercellular adhesion molecule-1 in GaAs-exposed mice were significantly below VH (36, 18 and 18%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

气管内单次给予砷化镓(GaAs;200毫克/千克)24小时,已被证明会抑制抗体产生以及其他T细胞介导的免疫功能。砷化镓还被证明对抗体形成细胞反应早期发生的事件具有毒性作用,这可能包括淋巴细胞活化和增殖。开展研究以确定砷化镓暴露是否导致T和B淋巴细胞无法对抗抗原刺激进行增殖。在用绵羊红细胞进行体外免疫后的最初24小时内,与载体(0.05%吐温80生理盐水溶液;VH)对照组相比,暴露于砷化镓的脾细胞增殖能力受到51%的抑制。VH组和砷化镓暴露组培养物之间的簇分化(CD)8+细胞绝对数量没有显著差异。然而,在用绵羊红细胞免疫24小时后评估的CD4+细胞数量减少了50%,并在为期5天的培养期内持续存在。分离T细胞和B细胞并分析其对各种促有丝分裂刺激的增殖能力。分离的B细胞在对脂多糖或抗免疫球蛋白加白细胞介素-4的增殖能力方面,VH组和砷化镓暴露组细胞之间没有差异。然而,与VH组相比,暴露于砷化镓的分离T细胞对刀豆球蛋白A、植物血凝素和抗CD3ε加白细胞介素-2的增殖能力受到显著抑制。此外,砷化镓暴露小鼠中CD25、白细胞功能抗原-1和细胞间黏附分子-1的表达明显低于VH组(分别为36%、18%和18%)。(摘要截短于250字)

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