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.
Article PDF
Similar content being viewed by others
References
J. Chang, R. Freer, R. Stella andL.M. Greenbaum,Studies on the Formation, Partial Amino Acid Sequence and Chemical Properties of Leukokinins M and PMN, Biochem. Pharmac.21, 3095 (1972).
R. Freer, J. Chang andL.M. Greenbaum,Pharmacological Activities of Leukokinins M and PMN, Biochem. Pharmac.21, 3107 (1972).
L.M. Greenbaum,Leukocyte Kininogenases and Leukokinins from Normal and Malignant Cells, Am. J. Path.68, 613 (1972).
M. Johnston andL.M. Greenbaum,Leukokinin-Forming System in the Ascitic Fluid of a Murine Mastocytoma, Biochem. Pharmac.22, 1386 (1973).
H. Umezawa et al.,Pepstatin, a New Inhibitor Produced by Actinomycetes, J. Antibiot.23, 259 (1970).
Author information
Authors and Affiliations
Additional information
Supported by a grant from the American Cancer Society and grants GM00438, CA 13061, USPHS.
Rights and permissions
About this article
Cite this article
Greenbaum, L.M., Prakash, A., Semente, G. et al. The leukokinin system; Its role in fluid accumulation in malignancy and inflammation. Agents and Actions 3, 332–334 (1973). https://doi.org/10.1007/BF01986490
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01986490