HAGEMAN TRAIT STUDIES

本申请中描述的研究旨在扩展我们的 了解Hageman因子（HF）在体内的作用。 Hageman因子 （凝血因子XII）可以在体外启动蛋白水解途径， 导致凝血，纤维蛋白溶解，激肽形成，趋化活性， 和补体激活[Ratnoff综述，1979（10），1983（11）]。 然而，Hageman因子在体内的作用仍然难以捉摸。 先前 报告提出了HF和接触激活系统可能 在某些条件下，在体内具有止血、血栓形成 纤维蛋白溶解、异物反应、炎症、休克、内毒素血症， 败血症、过敏反应和其他病症。 开始学习角色 HF在体内，我们已经设计了几个实验，利用一个独特的 资源，HF缺乏的猫。 我们将评估HF缺乏的影响 1）Shwartzman反应，2）Arthus反应，3） 白细胞趋化性（琼脂糖下的皮肤窗），4）肉芽肿形成， （5）过敏反应。 所有实验的核心将是建立一个更遗传的 按杂合子对杂合子的同质对照猫种群 育种 这些猫将在所有实验中用作对照动物， 也会成为传染源的哨兵 哈格曼特质小猫，但不是正常的随机源小猫，经验 增加对革兰氏阴性细菌感染的易感性（7）， 可能与HF缺乏或近亲繁殖有关。 广泛的记录 所有的疾病将继续，小猫将被监测， Hageman因子、溶血性补体、临床病理学的测量， 细菌培养、尸检和组织病理学检查。 一个 铜绿假单胞菌的实验性细菌内接种 HF缺乏和正常Hageman背景的小猫。

The research described in this application is intended to expand our knowledge on the role(s) of Hageman factor (HF) in vivo. Hageman factor (coagulation factor XII) can initiate proteolytic pathways in vitro which result in clotting, fibrinolysis, kinin formation, chemotactic activity, and complement activation [reviewed by Ratnoff, 1979 (10), 1983 (11)]. However, the role of Hageman factor in vivo remains elusive. Previous reports raise the possibility that HF and the contact activation system may have a role in vivo, under certain conditions, in hemostasis, thrombosis, fibrinolysis, foreign body reactions, inflammation, shock, endotoxemia, septicemia, anaphylaxis, and other conditions. To begin to study the role of HF in vivo, we have designed several experiments utilizing a unique resource, HF deficient cats. We will evaluate the effect of HF deficiency in development of 1) the Shwartzman reaction, 2) Arthus reaction, 3) leukocyte chemotaxis (skin windows under agarose), 4) granuloma formation, and 5) anaphylaxis. Central to all experiments will be the establishment of a more genetically homogeneous control cat population by heterozygote to heterozygote breeding. These cats will be used as control animals in all experiments, and will serve as sentinels for infectious agents as well. Hageman trait kittens, but not normal random source kittens, experience an increased susceptibility to gram-negative bacterial infections (7) which may be related either to HF deficiency or to inbreeding. Extensive records of all illnesses will be continued, and the kittens will be monitored by measurement of Hageman factor, hemolytic complement, clinical pathology, bacterial cultures, necropsy, and histopathology as indicated. An experimental intratracheal inoculation of Pseudomonas aeruginosa organisms into HF deficient and normal Hageman-background kittens is designed.