Kallikrein as a pathogenic agent in Plasmodium knowlesi infection in Macaca mulatta.

Methods for the fractionation and estimation of serum kallikrein in the blood of healthy and rhesus monkeys infected with Plasmodium knowlesi are discussed. A total mean increase of 4·5 ng. bradykinin equivalents/μg. protein content of kallikrein was shown to be present in the systemic circulation in the P. knowlesi-infected animal. A remarkable fall in the bradykininogen (BKG) content in infected animal is also observed. The kallikrein from an infected animal is observed to be more active than that from control in enhancing capillary permeability, and in the development of small vessels damage including diapedesis and haemorrhage. This action of kininogenase is unaffected by prior treatment of guinea-pig with anti-histamine drugs, but is almost blocked if kallikrein is incubated with protease inhibitors before i.d. injection. The action of kallikrein would suggest a 2-fold effect; that is, acting directly on the vessel walls and is also mediated by the release of kallidin (or kinin) from the precursor. Kallikrein fraction 4a, present only in the infected monkey, was found to be very active in initiating inflammatory reactions. The gross reduction in BKG level or its disappearance in the circulation in infected animals would invariably suggest a large turnover of kinins, but this latter substance is yet to be determined. The kininogenase from both healthy and infected animals produced hypotension in rabbits when injected i.v. at a relatively low dose. It is concluded that the increase in kallikrein concentration contemporaneous with the fall of kininogen in malarial infection (and possibly with increase in kinin or kallidin content) are concerned in the inflammatory phenomena involved in the pathogenesis of malaria.