PATHOGENESIS AND TREATMENT OF EXPERIMENTAL PERITONITIS

继发性细菌性腹膜炎仍然是一个难题 患者和外科医生。 即使新型抗生素出现， 死亡率几乎没有改善。 内部之内 腹膜腔环境中，宿主防御机制通常应该 起到限制入侵微生物的生长和扩散的作用。 我们寻求 为了更好地了解这些宿主防御 细胞水平以及整个动物。 特别是，目标 这项资助的目的是 1) 定义增强效应的机制 血红蛋白在实验性腹膜炎中的具体作用，2）确定 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 血红蛋白允许某些大肠杆菌菌株进化的观点 白细胞毒素可抑制中性粒细胞的杀菌功能 单核细胞。 这反过来又允许细菌增殖至致命 水平。 在第二种情况下，纤维蛋白及其分解产物会损害 中性粒细胞和单核细胞的杀菌功能不同 机制，即通过限制细菌的接触来削弱细菌的接触 宿主细胞迁移与细菌接触。 为了测试这些 假设，体内和体外技术都是必要的。 对于 第一个目标，基本策略是隔离和表征那些 细菌与血红蛋白相互作用的产物，会损害 中性粒细胞的体外功能。 然后这些材料将在老鼠身上进行测试 因为它们能够增强细菌菌株的感染， 不能用血红蛋白本身来增强。 对于第二个目标，我们计划 区分纤维蛋白对中性粒细胞的物理截留， 它对中性粒细胞的化学作用及其改变 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.