PATHOGENESIS AND TREATMENT OF EXPERIMENTAL PERITONITIS

继发性细菌性腹膜炎仍然是一个难题， 病人和外科医生都是。 即使有了新的抗生素， 死亡率几乎没有改善。 在内部 在腹膜腔的环境中，宿主的防御机制通常应该 限制入侵微生物的生长和扩散。 我们寻求 为了更好地了解这些宿主的防御， 细胞水平以及整个动物。 特别是， 这种补助金是1）确定增强作用的机制， 血红蛋白在实验性腹膜炎，2）以确定具体行动 纤维蛋白原和纤维蛋白在实验性腹膜炎和腹膜内 脓肿形成。 在第一种情况下，现有证据支持 血红蛋白允许某些E.大肠杆菌来阐述 抑制嗜中性粒细胞杀菌功能的白细胞毒素， 单核细胞 这反过来又使细菌增殖到致命的程度， 程度. 在第二种情况下，纤维蛋白及其分解产物损害了 嗜中性粒细胞和单核细胞的杀菌功能通过不同的 机制，即通过限制细菌的生长来损害细菌的进入。 宿主细胞迁移与细菌接触。 测试这些 假设，无论是在体内和体外技术将是必要的。 为 第一个目标，基本策略是分离和描述那些 细菌和血红蛋白之间相互作用的产物， 体外中性粒细胞功能。 这些材料将在大鼠中进行测试 因为它们能够增强细菌菌株的感染， 不能被血红蛋白本身增强。 对于第二个目标，我们计划 为了区分嗜中性粒细胞被纤维蛋白的物理截留， 其对中性粒细胞的化学作用及其对中性粒细胞的 生理环境

Secondary bacterial peritonitis continues to be a difficult problem for both patient and surgeon. Even with the advent of newer antibiotics, little improvement in mortality has been achieved. Within the internal milieu of the peritoneal cavity, host defense mechanisms normally should act to limit the growth and dispersion of invading microorganisms. We seek to obtain a better understanding of these host defenses both at the cellular level as well as in the entire animal. In particular, the aims of this grant are 1) to define the mechanism of the potentiating effect of hemoglobin in experimental peritonitis, 2) to determine the specific action of fibrinogen and fibrin in experimental peritonitis and intraperitoneal abscess formation. In the first case, the present evidence supports the idea that hemoglobin permits certain strains of E. coli to elaborate leukotoxins which inhibit the bacteriocidal function of neutrophils and monocytes. This, in turn, permits the bacteria to proliferate to lethal levels. In the second, fibrin and its breakdown products impair the bacteriocidal function of neutrophils and monocytes by a different mechanism, i.e. by impairing access to the bacteria by limiting the migration of host cells into contact with bacteria. To test these hypotheses, both in vivo and in vitro techniques will be necessary. For the first aim, the basic strategy is to isolate and characterize those products of the interaction between bacteria and hemoglobin which impair neutrophil function in vitro. These materials will then be tested in rats for their capacity to potentiate infections with bacterial strains which cannot be potentiated with hemoglobin itself. For the second aim, we plan to differentiate between the physical entrapment of neutrophils by fibrin, its chemical effects on the neutrophil and its alteration of the physiological milieu.