Laboratories of The Rockefeller Institute for Medical Research.
J Exp Med. 1927 Jul 31;46(2):315-41. doi: 10.1084/jem.46.2.315.
In this series of rabbits it was found that the rabbits dying during the 1st month after an injection of I or 2 mg. of bovine tubercle bacilli show the same conditions: extreme tuberculosis of the lungs, acute splenic tumor with tuberculosis, involvement of the lymph glands, an occasional small tubercle in the liver and extensive tuberculosis of the bone marrow. The peripheral blood has shown a sharp fall in the platelet count, an anemia and a fall in the granulocytic strain of white cells, and these changes have been correlated with the condition of the bone marrow. There has also been a rise in monocytes and a fall in lymphocytes, to a reversal of the normal ratio. When the rabbits have survived the first acute phase of the disease longer than 3 to 4 weeks, there have been signs in the peripheral blood of a recovery of the bone marrow; the first indication of this has been an increase in platelets, then a rise in hemoglobin followed in 1 or 2 days by a rise in red cells and later a return of the three strains of granulocytes. The bone marrow has shown a rapid spontaneous disintegration of the epithelioid cells correlated with the appearance of increased evidence of acid-fast debris in clasmatocytes, especially clear in those that lie along the vessels. The animals that have survived into the 3rd month have all shown a hyperplastic phase of the healing marrow, both the red cells and all types of the granulocytes appearing in the peripheral blood in numbers above the normal. The epithelioid cells originally containing many bacilli all disappear from the marrow and the only sign left, possibly suggestive of the tuberculosis, is the acid-fast granules in the clasmatocytes. Finally, the marrow becomes entirely normal, giving the normal number of red cells and granulocytes to the blood. Thus, bone marrow in the rabbit has become involved in every instance with the injection of massive doses of viable bacilli. The findings at autopsy in those animals followed during the early reaction to infection confirm this directly and, since the curves of the cells in the peripheral blood of the more chronic animals were the same during the early stages of the disease as in those that died, the same conclusion seems justified from indirect inference for them. The method of healing has been a rapid disintegration of the epithelioid cells without caseation. The bone marrow heals itself entirely regardless of the progress of the disease elsewhere, so that one sees the remarkable condition of an animal recovering from the anemia and leucopenia while dying of tuberculosis elsewhere. The spleen also shows a tendency toward spontaneous healing. In the animals that have lived beyond 100 days there has been some gradual lessening of the diffuse distribution and extent of pulmonary lesions with the development of cavitation together with a marked involvement of the kidneys and lesions in the eyes.
在这一系列兔子中,我们发现注射了 1 或 2 毫克牛结核杆菌的兔子,在注射后的第 1 个月内死亡,其肺部结核极为严重,脾脏急性肿瘤合并结核,淋巴结受累,肝脏偶尔出现小结核灶,骨髓广泛结核。外周血血小板计数急剧下降,出现贫血和粒细胞减少症,这些变化与骨髓状况相关。单核细胞增多,淋巴细胞减少,导致正常比例颠倒。当兔子在疾病的第一急性阶段存活超过 3 到 4 周时,外周血中骨髓有恢复的迹象;这首先表现为血小板增加,然后血红蛋白升高,随后 1 或 2 天红细胞升高,随后三种粒细胞恢复。骨髓中上皮样细胞迅速自发解体,与含酸染色体中可见的抗酸碎片增加相关,特别是沿着血管的那些更为明显。存活到第 3 个月的动物都表现出愈合骨髓的增生期,外周血中红细胞和所有类型的粒细胞数量均高于正常。最初含有许多杆菌的上皮样细胞均从骨髓中消失,唯一留下的迹象可能提示结核病,是含酸染色体中的抗酸颗粒。最后,骨髓完全恢复正常,使血液中的红细胞和粒细胞数量恢复正常。因此,在兔中,骨髓在注射大量活菌时都受到了影响。对那些在感染早期反应期间被跟踪的动物进行尸检的发现直接证实了这一点,并且由于慢性动物的外周血细胞曲线在疾病的早期阶段与死亡的动物相同,因此从间接推断来看,它们似乎也有同样的结论。愈合的方法是上皮样细胞迅速解体而无干酪样坏死。骨髓可以自行完全愈合,无论其他部位疾病的进展如何,因此人们会看到一只动物从贫血和白细胞减少症中恢复,而在其他地方死于结核病的显著情况。脾脏也有自发愈合的趋势。在存活超过 100 天的动物中,肺部病变的弥漫性分布和程度逐渐减轻,出现空洞形成,同时肾脏和眼睛也出现明显病变。