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皮质酮应激水平引起的骨髓淋巴细胞生成和粒细胞生成区室的快速变化。

Rapid changes in the lymphopoietic and granulopoietic compartments of the marrow caused by stress levels of corticosterone.

作者信息

Laakko Tonya, Fraker Pamela

机构信息

Department of Biochemistry and Molecular Biology,Michigan State University, East Lansing, Michigan 48824-1319, USA.

出版信息

Immunology. 2002 Jan;105(1):111-9. doi: 10.1046/j.1365-2567.2002.01346.x.

Abstract

Exposure to concentrations of glucocorticoids analogous to those produced during stress, trauma and malnutrition had rapid but varying effects on the major classes of cells within the marrow. Corticosterone (CS) was given as a subdermal implant in young mice and generated 60-95 microg CS/dl of blood compared to 5-15 microg CS/dl for sham controls over a period of 36 hr. Within 24 hr CS had caused losses of 30-70% among the early pro-B, pre-B and immature B cells. The pre-B cells were virtually eliminated by 36 hr and the capacity of surviving pro- and pre-B cells to cycle was reduced by 70-80%. Interestingly, the earliest of B cells, the prepro-B cells, showed considerable resistance to CS, being reduced by only 20% at 36 hr. Thus, the pattern of survival within the B-cell compartment paralleled the expression of Bcl-2. At the 36-hr time-point there were no changes in the proportion of progenitor cells, erythroid or monocytic cells, or number of nucleated cells in the marrow. By contrast, 36 hr after exposure to CS there was an increase of 30% in the proportion and absolute number of cells in the granulocytic compartment. Chronic production of CS appears to reprogramme lymphopoiesis and myelopoiesis, perhaps to preserve the first line of immune defence at the expense of the lymphoid branch. Resistance to apoptosis and modifications in the activity of the glucocorticoid receptor and cytokines produced by stromal cells are postulated as targets for CS-driven changes.

摘要

暴露于与应激、创伤和营养不良期间产生的浓度类似的糖皮质激素中,会对骨髓内的主要细胞类别产生迅速但各异的影响。给幼鼠皮下植入皮质酮(CS),在36小时内,血液中产生的CS为60 - 95微克/分升,而假手术对照组为5 - 15微克/分升。在24小时内,CS导致早期前B细胞、前B细胞和未成熟B细胞减少30 - 70%。到36小时时,前B细胞几乎被消除,存活的前B细胞和前B细胞的循环能力降低70 - 80%。有趣的是,最早的B细胞,即前前B细胞,对CS表现出相当的抗性,在36小时时仅减少20%。因此,B细胞区室中的存活模式与Bcl - 2的表达平行。在36小时时间点,骨髓中祖细胞、红系或单核细胞的比例以及有核细胞数量没有变化。相比之下,暴露于CS 36小时后,粒细胞区室中的细胞比例和绝对数量增加了30%。CS的长期产生似乎会重新编程淋巴细胞生成和髓细胞生成,可能是以淋巴分支为代价来维持免疫防御的第一线。对细胞凋亡的抗性以及基质细胞产生的糖皮质激素受体和细胞因子活性的改变被假定为CS驱动变化的靶点。

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