Samlowski W E, Johnson H M, Hammond E H, Robertson B A, Daynes R A
Lab Invest. 1987 Jan;56(1):85-95.
Gamma-irradiation has been extensively utilized as a bone marrow ablative agent during human bone marrow transplantation. Although the effects of ionizing radiation on lymphoid and hematopoietic cells are well documented, little is currently known about its effect on the nonhematopoietic tissues which are important for the restoration of normal immune function. The vast majority of lymphocyte movement into peripheral lymph nodes takes place via the bloodstream and requires a specific receptor-ligand interaction between the lymphocyte and anatomically distinct postcapillary venules. Due to the importance of lymphocyte recirculation in the initiation and amplification of immune responses, an understanding of the radiosensitivity of the postcapillary venules may provide insight into the pathogenesis of the immune deficiencies commonly seen after bone marrow transplantation. Our studies disclosed that the ability of normal blood-borne lymphocytes to enter peripheral lymph nodes was markedly depressed (less than 50% of normal) in mice which had been exposed to 7.5 Gy of gamma-irradiation. This radiation-induced effect lasted longer than 6 months after irradiation and syngeneic reconstitution, and its magnitude was radiation-dose dependent. Immunochemical staining of the lymph node microvasculature with the monoclonal antibody MECA-325 established that the radiation protocol induced persistent anatomic changes in the lymphocyte-receptive areas of endothelium (high endothelial venules). These vessels developed the appearance of endothelial cell proliferation. Electron microscopy demonstrated significant intracellular edema, with virtual occlusion of many microvascular lumens by edematous endothelial cells. Lymph nodes from human bone marrow transplant recipients were found to exhibit similar ultrastructural changes. These studies for the first time demonstrate that doses of irradiation similar to those used to prepare bone marrow transplant recipients can have significant anatomic and functional sequellae on host endothelial cells.
在人类骨髓移植过程中，γ射线已被广泛用作骨髓清除剂。尽管电离辐射对淋巴细胞和造血细胞的影响已有充分记载，但目前对于其对恢复正常免疫功能至关重要的非造血组织的影响却知之甚少。绝大多数淋巴细胞通过血液循环进入外周淋巴结，这需要淋巴细胞与解剖学上不同的毛细血管后微静脉之间特定的受体 - 配体相互作用。由于淋巴细胞再循环在免疫反应的启动和放大中具有重要作用，了解毛细血管后微静脉的放射敏感性可能有助于深入了解骨髓移植后常见的免疫缺陷的发病机制。我们的研究表明，在接受7.5 Gyγ射线照射的小鼠中，正常血源性淋巴细胞进入外周淋巴结的能力显著降低（不到正常水平的50%）。这种辐射诱导的效应在照射和同基因重建后持续超过6个月，其程度与辐射剂量相关。用单克隆抗体MECA - 325对淋巴结微血管进行免疫化学染色表明，辐射方案在内皮细胞（高内皮微静脉）的淋巴细胞接受区域诱导了持续的解剖学变化。这些血管出现了内皮细胞增殖的外观。电子显微镜显示有明显的细胞内水肿，许多微血管腔被水肿的内皮细胞几乎完全阻塞。在人类骨髓移植受者的淋巴结中也发现了类似的超微结构变化。这些研究首次表明，与用于准备骨髓移植受者的辐射剂量相似的辐射剂量可对宿主内皮细胞产生显著的解剖学和功能性后遗症。
