Degowin R L, Lass S L
J Lab Clin Med. 1985 Mar;105(3):299-304.
Our studies show that the induction of a chronic inflammatory lesion in the left hind legs of mice by administration of 5000 rad produced distinct abnormalities of the hematopoietic system. A peripheral neutrophilia accompanied reduced numbers of total nucleated cells, stem cells, stromal cells, erythroblasts, and lymphocytes in the unirradiated femoral marrow, and the spleen was enlarged. Mice with these hematopoietic abnormalities promptly succumbed with bone marrow failure to a sublethal dose of total body irradiation (600 rad TB). Acute inflammation associated with a sterile abscess also impaired survival after 600 rad TB. Hematopoietic abnormalities resembling those in mice with inflammation had been reported in mice bearing a solid extramedullary tumor of sarcoma-180. Concomitant studies showed that bone marrow failure and impaired survival after 600 rad TB administered to mice bearing sarcoma-180 occurred at the same time as that in mice with chronic inflammation. We concluded that chronic inflammation or tumor produced similar abnormalities in the bone marrow and spleen that led to markedly impaired survival and death from bone marrow failure after a sublethal dose of total body irradiation. Although the extramedullary hematopoiesis in the enlarged spleen indicated that its microenvironment supported hematopoiesis, whereas that in marrow was reduced, it was insufficient to compensate for a total body deficit of functional stem cells.
我们的研究表明，给小鼠左后肢给予5000拉德辐射以诱导慢性炎症性病变，会导致造血系统出现明显异常。外周血中性粒细胞增多，同时未受辐射的股骨骨髓中总核细胞、干细胞、基质细胞、成红细胞和淋巴细胞数量减少，且脾脏肿大。出现这些造血异常的小鼠会因骨髓衰竭迅速死于亚致死剂量的全身照射（600拉德全身照射）。与无菌性脓肿相关的急性炎症也会损害600拉德全身照射后的存活率。在患有肉瘤-180实体髓外肿瘤的小鼠中，曾报道过与炎症小鼠类似的造血异常。同时进行的研究表明，给患有肉瘤-180的小鼠给予600拉德全身照射后，骨髓衰竭和存活率受损的情况与慢性炎症小鼠同时出现。我们得出结论，慢性炎症或肿瘤在骨髓和脾脏中产生了类似的异常，导致在亚致死剂量的全身照射后，存活率显著受损并因骨髓衰竭而死亡。尽管肿大脾脏中的髓外造血表明其微环境支持造血，而骨髓中的造血则减少，但这不足以弥补功能性干细胞的全身短缺。
