Structure and function of bone marrow hemopoiesis: Mechanisms of response to ionizing radiation exposure
Structure and function of bone marrow hemopoiesis: Mechanisms of response to ionizing radiation exposure
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DOI：
10.1089/108497802760363204
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发表时间：
2002-08-01
影响因子：
3.4
通讯作者：
Reimers, K
中科院分区：
文献类型：
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作者：
Fliedner, TM;Graessle, D;Reimers, K
这是本报告的目的，审查的独特结构和功能的骨髓锚定造血的意义，其响应机制暴露于电离辐射。骨髓造血的最终目的是在外周血中维持不同血细胞类型（红细胞、粒细胞、血小板、淋巴细胞等）的恒定水平。它们都具有其特定的周转动力学（例如粒细胞120 × 10（9）/d，红细胞200 × 10（9）/d或血小板150 × 10（9）/d），在其稳态调节机制中是半自主的，并且依赖于来自具有无限复制和多能分化潜能的干细胞库的成熟细胞的终身供应。造血细胞更新的现有知识是多年使用各种代谢形式的放射性核素的基础实验和临床研究的结果，所述放射性核素包括Fe-59、P-32（DF P-32）、Cr-51、I-131、Co-60、H-3（（3）HTdR）和C-14（（14）CTdR）。为了了解生理学，特别是辐射病理生理学，必须详细认识骨髓作为一个独特单位的基础结构。终身细胞生产的基础是骨髓的囊-骨皮质-，血液的动脉供应连接到窦状微血管结构，其窦状肌和直肌以及中央（细胞收集）窦状肌。认识到以有髓和无髓神经纤维为特征的神经调节血流的重要性也是重要的。独特的窦状隙衬细胞类型。是造血实质和血液之间细胞运输的先决条件。如果没有正弦段的交替打开和关闭，这又不能实现，这又需要刚性的长胶囊来确保每个骨髓单位的总体积恒定。如果骨髓单位暴露于电离辐射，可以观察到细胞生长压力和血流动力学之间的平衡紊乱，导致特殊类型的骨髓出血和“过量细胞丢失”，这可能导致干细胞池的非血栓减少性耗尽。尽管骨髓单位分布在骨骼中的100多个骨髓区域或单位中，但允许骨髓造血作为一个细胞更新系统发挥作用的机制是非常重要的问题。"骨髓"作为"一个器官"起作用和反应的观察结果是由于调节机制：肱骨因子（如红细胞生成素、粒细胞生成素、血小板生成素等），神经因素（中枢神经调节）和细胞因素（干细胞通过血液的连续迁移以确保每个骨髓"亚单位"中有足够的干细胞池大小）。应该记得，骨髓作为生理嵌合体发挥作用，并在胚胎发生期间通过造血干细胞向间充质基质的接种而建立。局部照射后骨髓的再生，在强烈不均匀的辐射暴露后或在全身暴露后进行干细胞移植可以很好地被认为是骨髓造血的胚胎发生的重复，其中干细胞的关键要素通过血液迁移到准备接受干细胞回家并开始其复制的骨髓基质部位。造血需要对结构、功能和调节的生理学和病理生理学有透彻的理解，不仅是细胞更新的过程，而且是复杂的基础结构。
It is the purpose of this presentation to review the unique structure and function of bone marrow anchored hematopoiesis in their significance for its response mechanisms to an exposure to ionizing radiation. The ultimate objective of bone marrow hematopoiesis is to maintain in the peripheral blood a constant level of the different blood cell types (erythrocytes, granulocytes, platelets, lymphocytes, etc.). All of them have their particular turnover kinetics (such as granulocytes 120 X 10(9)/d, erythrocytes 200 X I 10(9)/d or thrombocytes 150 X 10(9)/d), are semi-autonomous in their steady state regulatory mechanisms and dependent on a life-long supply of mature cells from a stem cell pool with unlimited replicative and pluripotent differentiative potential. The present knowledge of hematopoietic cellular renewal is the result of years of basic experimental and clinical studies using radionuclides in various metabolic forms including Fe-59, P-32 (DF P-32), Cr-51, I-131, Co-60, H-3 ((3)HTdR) and C-14 ((14)CTdR). To understand the physiology but in particular the radiation-pathophysiology, it is essential to recognize in detail the infrastructure of the bone marrow as a distinct unit. Indispensable for a life-long cell production is the capsule of the marrow-the bone cortex-, the arterial supply of blood connected to the sinusoidal microvascular architecture with its sinusoids contorti and recti as well as the central (cell collecting) sinusoids. It is further of importance to recognize the significance of nerval regulation of blood flow, characterized by myelinated and unmyelinated nerve fibers. The type of unique lining cells of the sinusoids. is the prerequisite for the cell traffic between the hemopoietic parenchyma and the blood. This in turn cannot be achieved without an alternative opening and closing of the sinusoidal segments which-in turn-requires a rigid long capsule to assure an-in toto-constant volume of each bone marrow unit. If a bone marrow unit is exposed to ionizing radiation, a perturbance of the balance between cellular growth pressure and blood flow dynamics can be observed, resulting in a special type of bone marrow hemorrhage and an "excess cell loss" that may result in an non-thrombopenic exhaustion of the stem cell pool. Of great importance is the question as to the mechanisms that allow the bone marrow hemopoiesis to act as one cell renewal system although the bone marrow units are distributed throughout more than 100 bone marrow areas or units in the skeleton. The observation that "the bone marrow" acts and reacts as "one organ" is due to the regulatory mechanisms: the humeral factors (such as erythropoietins, granulopoietins, thrombopoietins etc.), the nerval factors (central nervous regulation) and cellular factors (continuous migration of stem cells through the blood to assure a sufficient stem cell pool size in each bone marrow "sub-unit"). It should be recalled that the bone marrow functions as a physiological chimera and becomes established by the hematogeneic seeding of stem cells to a mesenchymal matrix during embryogenesis. The repopulation of the bone marrow after partial body irradiation, after strongly inhomogeneous radiation exposure or after total body exposure with stem cell transplantation can well be considered as a repetition of the embryogenesis of bone marrow hemopoiesis with the key element of stem cells migrating via the blood to stromal sites of the marrow prepared to accept stem cells to home and start their replIn summary the radiation biology of bone marrow hemopoiesis requires a thorough understanding of the physiology and pathophysiology of structure, function and regulation not only of the process of cellular renewal but also of the intricate infrastructure.