HAGEMAN TRAIT STUDIES

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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.