Endotoxemia down-regulates bone marrow lymphopoiesis but stimulates myelopoiesis: the effect of G6PD deficiency
Endotoxemia down-regulates bone marrow lymphopoiesis but stimulates myelopoiesis: the effect of G6PD deficiency
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DOI：
10.1189/jlb.1207838
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发表时间：
2008-06-01
影响因子：
5.5
通讯作者：
Spolarics, Zoltan
中科院分区：
文献类型：
--
作者：
Chandra, Rachna;Villanueva, Erika;Spolarics, Zoltan
骨髓（BM）功能障碍是免疫调节的重要组成部分。本研究调查了内毒素血症小鼠（大肠杆菌LPS）骨髓、血液和脾脏中细胞含量、凋亡反应和细胞增殖的变化。由于与葡萄糖-6-磷酸脱氢酶（G6 PD）缺乏相关的抗氧化状态降低已被证明可调节先天性免疫反应，我们还测试了G6 PD突变（细胞酶活性降低80%）是否会改变内毒素血症期间的BM反应。与对照组相比，LPS降低BM髓系（CD 45（+）CD 11 B（+））和B淋巴（CD 45（+）CD 19（+）CD 11 B（-））细胞含量。相反，LPS增加CD 11 B（+）髓样细胞，但减少循环中的T和B细胞计数。内毒素血症抑制自发性，热休克，和H2 O2诱导的细胞凋亡以及骨髓淋巴细胞的增殖活性。与此相反，骨髓细胞凋亡没有改变，他们的增殖活性增加，在内毒素血症。LPS后，脾髓样细胞含量增加，T和B细胞含量无变化;此外，脾细胞凋亡与对照组相比增加。BM细胞含量，包括淋巴细胞和骨髓细胞，在G6 PD突变型小鼠中比野生型（WT）小鼠更大，并且LPS在突变型小鼠中比WT小鼠更大程度地降低BM细胞计数。内毒素血症引起广泛的抑制BM细胞因子和趋化因子的生产，但是，IL-6的生产相比，对照组增加。与WT相比，G6 PD突变动物中LPS诱导的IL-6产生减少。这项研究表明，内毒素反向影响骨髓和淋巴细胞的生产。LPS诱导的B细胞产生的下调导致非特异性免疫攻击后观察到的全身淋巴细胞减少症和淋巴细胞功能障碍。
Bone marrow (BM) dysfunction is an important component of immunomodulation. This study investigated alterations in cell content, apoptotic responses, and cell proliferation in BM, blood, and spleen in endotoxemic mice (LPS from Escherichia coli). As the decreased antioxidant status associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to modulate the innate immune response, we also tested whether a G6PD mutation (80% decrease in cellular enzyme activity) alters BM responses during endotoxemia. LPS decreased BM myeloid (CD45(+) CD11b(+)) and B lymphoid (CD45(+) CD19(+) CD11b(-)) cell content compared with controls. In contrast, LPS increased CD11b(+) myeloid but decreased T and B cell counts in the circulation. Endotoxemia inhibited spontaneous, heat shock, and H2O2-induced apoptosis as well as proliferative activity in BM lymphoid cells. In contrast, BM myeloid cell apoptosis was not altered, and their proliferative activity was increased during endotoxemia. Following LPS, splenic myeloid cell content was increased, and T and B cell content was unchanged; furthermore, splenocytes showed increased apoptosis compared with controls. BM cell content, including lymphoid and myeloid cells, was greater in G6PD mutant than wild-type (WT) mice, and LPS decreased BM cell counts to a greater degree in mutant than WT mice. Endotoxemia caused widespread inhibition of BM cytokine and chemokine production; however, IL-6 production was increased compared with controls. LPS-induced IL-6 production was decreased in G6PD mutant animals compared with WT. This study indicates that endotoxin inversely affects BM myeloid and lymphoid cell production. LPS-induced down-regulation of B cell production contributes to the generalized lymphopenia and lymphocyte dysfunction observed following nonspecific immune challenges.