PATHOGENESIS AND TREATMENT OF EXPERIMENTAL PERITONITIS

继发性细菌性腹膜炎仍然是一个难题 包括病人和外科医生。即使出现了新的抗生素， 死亡率几乎没有改善。在内部 腹膜腔周围环境，宿主防御机制通常应 采取行动限制入侵微生物的生长和扩散。我们在寻找 为了更好地了解这些主机防御， 细胞水平和整个动物的水平。特别是，它的目标是 这项授权是1)定义增强作用的机制 血红蛋白在实验性腹膜炎中的作用2)特异性测定 纤维蛋白原和纤维蛋白在实验性腹膜炎和腹膜腔内的变化 脓肿形成。在第一个案例中，目前的证据支持 认为血红蛋白允许某些大肠杆菌菌株详细说明 抑制中性粒细胞杀菌功能的白细胞毒素和 单核细胞。这反过来又允许细菌繁殖到致命的程度 级别。在第二种情况下，纤维蛋白及其分解产物会损害 不同种类中性粒细胞和单核细胞的杀菌作用 机制，即通过限制细菌的接触而损害对细菌的获取 宿主细胞迁移到与细菌接触的地方。为了测试这些 体内和体外技术的假设都是必要的。为 第一个目标，基本策略是分离和表征这些 细菌与血红蛋白相互作用的产物 体外培养中性粒细胞功能。然后，这些材料将在老鼠身上进行测试 因为它们有能力加强对细菌菌株的感染 不能用血红蛋白本身来增强。对于第二个目标，我们计划 为了区分纤维蛋白对中性粒细胞的物理包裹， 其对中性粒细胞的化学作用及其对中性粒细胞的影响 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.