The leukokinin system; its role in fluid accumulation in malignancy and inflammation.

Abstract

Leukokinins are peptides having 20–25 amino acids. They are formed by acid proteases contained in leukocytes, cancer cells, and ascites fluids acting on a protein substrate known as leukokininogen. The leukokinins do not contain the bradykinin sequence in their molecule. The leukokinins are extremely potent (even more so than bradykinin) in causing increased vascular permeability and hypotensive blood pressure changes. The substrate from which leukokinins are cleaved, leukokininogen is ‘not’ a normal constituent of plasma, but is formed in certain pathological conditions in plasma or in pathological fluids from a ‘proleukokininogen’. This conversion is the limiting step in the availability of leukokinins. While all white cells so far tested contain cathepsins D- and E-like enzymes which act as leukokininogenases (form leukokinins), the white cells do ‘not’ contain kallikreins and consequently do not form bradykinin. The leukokinin system may represent the system which generates fluid accumulation in pathology such as ascites of neoplastic disease, arthritis and inflammation. Strong proof of this is seen in the experiments to be described in which an inhibitor of leukokinin formation, in vitro, ‘Pepstatin’ retards and even prevents ascites fluid accumulation in mice in vivo.