Medical Clinic of the Peter Bent Brigham Hospital, Boston.
J Exp Med. 1916 Oct 1;24(4):315-27. doi: 10.1084/jem.24.4.315.
Cultures of Streptococcus viridans when brought into contact with red blood corpuscles have the power of transforming oxyhemoglobin into methemoglobin. The reaction occurs only in the presence of living streptococci when they are able to carry on their metabolic activities. The intensity of the reaction runs roughly parallel with the period of growth and multiplication of the bacteria and gradually diminishes and disappears as growth ceases. There is no apparent relation between the activity of a given strain of Streptococcus viridans in producing methemoglobin and its source or virulence. If the streptococci are suspended in salt solution they are unable to change oxyhemoglobin into methemoglobin unless some nutrient substance is present. Of the various nutrient substances tested dextrose is the most efficient in enabling the organisms to bring about the reaction. The reaction does not occur in the absence of oxygen, and is retarded by an excess of oxygen. Substances which tend to reduce the metabolic activities of the bacteria to a minimum exert an inhibitory action on methemoglobin formation. While not definitely proving it to be so, the results obtained in the above experiments strongly support the supposition that the reaction is not due to injurious substances produced by the bacteria or to products arising from the decomposition of the nutrient material present, but rather to the metabolic activities of the bacteria themselves when they are surrounded by environmental conditions which render growth and multiplication possible. The exact chemical nature of the change of oxyhemoglobin to methemoglobin is not known, but it is probably an oxidation process or a combination of reduction and oxidation processes, as pointed out by Heubner. As Cole has shown, the action of aminophenol is of great interest in this connection, in that it acts like a catalytic agent in being able to transform much more hemoglobin into methemoglobin than would be possible if the reaction were a simple molecular one. The metabolic activities of bacteria are largely in the nature of oxidation and reduction processes. The transformation of oxyhemoglobin into methemoglobin by streptococci of the viridans type, therefore, may be analogous to the action of such substances as aminophenol, and the reaction may be due to the active oxidation and reduction processes occurring in the neighborhood of the bacterial cells. The failure of the reaction to occur in the absence of oxygen and its retardation in the presence of an excess of oxygen, both with streptococci and with pneumococci (Cole) would seem to support this theory. Such results, however, may be due to the abnormal conditions surrounding the bacteria with consequent inhibition of their metabolic activities. Cole concluded as the result of his study of methemoglobin formation by pneumococci that since bacteria may injure red blood cells apparently by disturbances in oxidation in the immediate neighborhood of the organisms rather than by the production of a definite toxin, it is possible that bacteria may injure other tissue cells in a like manner and that the pathological effects produced by these bacteria may be explained on this basis. The experimental results recorded above have shown that the formation of methemoglobin by Streptococcus viridans in no way differs from its formation by pneumococci, and they lend support to the theory that bacteria may be injurious to tissues because of the disturbances in oxidation brought about by the metabolic activities of the organisms, especially those associated with growth and multiplication. It is believed that this theory may be particularly applicable to the pathological effects caused by Streptococcus vindans because the lesions produced by it, whether single or multiple, both in man and in experimental animals, are prone to be localized and associated with the actual presence of the streptococci in the lesions.
草绿色链球菌与红细胞接触时,具有将氧合血红蛋白转化为高铁血红蛋白的能力。只有当活链球菌能够进行新陈代谢活动时,这种反应才会在它们存在的情况下发生。反应的强度大致与细菌生长和繁殖的时期平行,并随着生长的停止而逐渐减弱和消失。在给定的草绿色链球菌产生高铁血红蛋白的活性与其来源或毒力之间没有明显的关系。如果链球菌悬浮在盐溶液中,除非存在某些营养物质,否则它们无法将氧合血红蛋白转化为高铁血红蛋白。在测试的各种营养物质中,葡萄糖是最有效地使生物体发生反应的物质。反应不会在没有氧气的情况下发生,并且氧气过量会使其受到抑制。那些倾向于将细菌的代谢活动降至最低的物质对高铁血红蛋白的形成具有抑制作用。虽然不能明确证明这一点,但上述实验的结果强烈支持这样一种假设,即该反应不是由细菌产生的有害物质或由存在的营养物质分解产生的产物引起的,而是由细菌自身的代谢活动引起的,当它们处于有利于生长和繁殖的环境条件下时。氧合血红蛋白向高铁血红蛋白的转化的确切化学性质尚不清楚,但正如休布纳所指出的,它可能是氧化过程或还原和氧化过程的组合。正如科尔所表明的,氨基苯酚的作用在这方面非常有趣,因为它能够将更多的血红蛋白转化为高铁血红蛋白,而不是如果反应是简单的分子反应可能的。细菌的代谢活动在很大程度上是氧化和还原过程。因此,草绿色链球菌将氧合血红蛋白转化为高铁血红蛋白的作用可能类似于氨基苯酚等物质的作用,并且该反应可能是由于细菌细胞附近发生的活性氧化和还原过程引起的。链球菌和肺炎球菌(科尔)的反应在没有氧气的情况下不会发生,并且在氧气过量的情况下会受到抑制,这似乎支持了这一理论。然而,这些结果可能是由于细菌周围的异常情况导致其代谢活动受到抑制所致。科尔在研究肺炎球菌高铁血红蛋白形成后得出结论,由于细菌显然可以通过生物体附近的氧化紊乱而不是通过产生特定的毒素来损伤红细胞,因此细菌也可能以类似的方式损伤其他组织细胞,并且这些细菌产生的病理效应可以在此基础上得到解释。上述实验结果表明,草绿色链球菌形成高铁血红蛋白的方式与肺炎球菌完全不同,这支持了这样一种理论,即细菌可能由于其代谢活动引起的氧化紊乱而对组织造成伤害,特别是与生长和繁殖相关的活动。据信,该理论可能特别适用于草绿色链球菌引起的病理效应,因为它在人和实验动物中产生的病变无论是单一的还是多个的,都容易局限于并与链球菌在病变中的实际存在相关。