SPLENIC CELL TARGETS IN GALLIUM ARSENIDE-INDUCED SUPPRESSION OF THE PRIMARY ANTIBODY-RESPONSE
SPLENIC CELL TARGETS IN GALLIUM ARSENIDE-INDUCED SUPPRESSION OF THE PRIMARY ANTIBODY-RESPONSE
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DOI：
10.1016/0041-008x(91)90296-q
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发表时间：
1991-08-01
影响因子：
3.8
通讯作者：
MUNSON, AE
中科院分区：
文献类型：
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作者：
SIKORSKI, EE;BURNS, LA;MUNSON, AE
以雌性B6C3F1小鼠为研究对象，研究了砷化镓对小鼠体外免疫球蛋白M抗体形成细胞(AFC)应答的影响。体内暴露于气管内单次剂量的砷化镓(2.5-200 mg/kg)可导致体外对T依赖抗原绵羊红细胞(SRBC)的IgM AFC反应呈剂量依赖性下降，200 mg/kg剂量组与赋形剂对照组相比下降97%。100 mg/kg和200 mg/kg剂量组小鼠对T非依赖性抗原DNP-Ficoll的反应显著降低。小鼠脾细胞数随剂量增加而降低，200 mg/kg剂量组小鼠脾细胞数下降54%。脾细胞计数结果显示，Thy1.2(T细胞)、Ig(B细胞)和F4-80(巨噬细胞)阳性细胞总数分别减少了58、61和30%，而这些细胞的百分比没有改变。暴露于砷化镓的小鼠脾细胞的有丝分裂反应性没有改变。为了确定以砷化镓为靶点的脾细胞群，在分离/重建来自砷化镓(200 mg/kg，24小时暴露)和车辆暴露的小鼠的脾细胞后，评估了SRBC对AFC的反应。结果表明，AFC抑制是由于粘附性(AD；巨噬细胞)和非粘附性(T和B淋巴细胞)细胞群的功能改变所致。进一步的调查集中在AD人群的变化上。分离/重建实验表明，AFC对SRBC的抑制作用依赖于暴露于砷小鼠的巨噬细胞的浓度。这种巨噬细胞介导的体外AFC反应的抑制不能归因于抑制性巨噬细胞的存在或前列腺素的释放。
In vivo exposure of female B6C3F1 mice to gallium arsenide (GaAs) was evaluated for its effect on the in vitro IgM antibody-forming cell (AFC) response. In vivo exposure to a single intratracheal dose of GaAs (2.5–200 mg/kg) resulted in a dose-dependent decrease in the in vitro IgM AFC response to the T-dependent antigen sheep red blood cells (SRBC) with a 97% decrease at 200 mg/kg when compared to vehicle controls. The response to the T-independent antigen DNP-Ficoll was significantly reduced at 100 and 200 mg/kg. Spleen cellularity decreased in a dose-related manner with a 54% decrease at 200 mg/kg. Enumeration of splenic subpopulations following GaAs (200 mg/kg) indicated a 58, 61, and 30% decrease in the total number of Thy 1.2 (T cells), Ig (B cells), and F4 80 (macrophages) positive cells, respectively, with no alterations in the percentages of these cells. Mitogenic responsiveness of splenocytes from GaAs-exposed mice was unaltered. To identify the splenic cell populations targeted by GaAs, the AFC response to SRBC was evaluated following cell separation/reconstitution of splenocytes from GaAs- (200 mg/kg, 24-hr exposure) and vehicle-exposed mice. Results demonstrated AFC suppression was due to functional alterations in both adherent (AD; macrophages) and nonadherent, (both T and B lymphocytes) cell populations. Further investigation focused on alterations in the AD population. Separation/reconstitution experiments demonstrated AFC suppression to SRBC was dependent on the concentration of macrophages from GaAs-exposed mice. This macrophage-mediated suppression of the in vitro AFC response could not be attributed to the presence of suppressor macrophages or release of prostaglandins.