Abstract
Plasma kallikrein (PK) is a cofactor in blood coagulation and modulates inflammation through the release of bradykinin. Previously it was believed that plasma prekallikrein (PPK), the precursor of PK and a member of the serine protease superfamily, was synthesized exclusively by hepatocytes and secreted into circulation. However, recent studies show that the human brain contains a high level of PPK mRNA. In this study we sought to determine which areas of the brain express PK. Tissue from the spinal cord and 13 different regions of the human brain were collected at autopsy within 24h from death. Sections were probed using polyclonal antibodies (characterized by Western blotting) specific for PK. PK concentrations in extracts of these tissues were measured by ELISA. Immunolabeling of PK was observed in the cell bodies of the neurons of the hypothalamus, thalamus, spinal cord, cerebral cortex and brainstem. Positive PK immuno-reactivity was also demonstrated in the cytoplasm of the ependymal cells in sections of the hypothalamus and spinal cord. In addition, some fibre tracts of the pons, medulla and hippocampus as well as secretory cells of the pituitary gland also labeled. No immunoreactive PK was visualized in the choroid plexus or cerebellum. Our data demonstrate the cellular localization of PK in human brain. This work is supported by other studies that demonstrate PK mRNA in human heart, lung, trachea and brain. The cellular distribution of PK and kinin receptors in specific brain areas suggests a role for PK in the nervous system.
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REFERENCES
Bhoola, K.D., Figueroa, C.D., and Worthy, K. (1992). Bioregulation of kinins: kallikreins, kininogens and kininases. Pharmacol. Rev. 44:1-80.
Cerf, M.E., Raidoo, D.M., Fink, E., Fritz, H., and Bhoola, K.D. (1999). Plasma kallikrein localisation in human blood vessels. Immunopharm. 44:75-80.
Henderson, L.M., Figueroa, C.D., Müller-Esterl, W., Stain, A., and Bhoola, K.D. (1992). Immunovisualisation of plasma prekallikrein and H-kininogen on human neutrophils and in human hepatocytes. Agents Actions S38:590-594.
Hermann, A., Buchinger, P., Somlev, B., and Rehbock, J. (1996). High and low molecular weight kininogen and plasma prekallikrein/plasma kallikrein in villous capillaries of human term placenta. Placenta 17:223-230.
Hess, J.F., Borkowski, J.A., Young, G.S., Strader, C.D., and Ransom, R.W. (1992). Cloning and pharmacological characterization of a human bradykinin (BK 2) receptor. Biochem. Biophys. Res. Commun. 184:260-268.
Jones T.H., Figueroa, C.D., and Bhoola, K.D. (1992). Bioregulatory role of the kallikrein-kinin system in the normal pituitary gland and its tumors. Acta Endocrinol. 127:481-484.
Kaplan, A.P., Kay, A.B., and Austen, K.F. (1972). A prealbumin activator of prekallikrein III. Appearance of chemotactic activity for human neutrophil by the conversion of human prekallikrein to kallikrein. J. Exp. Med. 135:81-97.
Mandle, R., Jr., and Kaplan, A.P. (1977). Hageman factor substrates. II. Human plasma prekallikrein. Mechanism of activation by Hageman factor and participation in Hageman factor dependent fibrinolysis. J. Biol. Chem. 252:6097-6104.
Mandle, R., Jr., Colman, R.W., and Kaplan, A.P. (1976). Identification of prekallikrein and HMW-kininogen as a circulating complex in human plasma. Proc. Natl. Acad. Sci. U.S.A. 73:4179-4183.
Maier-Hauff, K., Baethmann, A.J., Lange, M., Schurer, L., and Unterberg, A. (1984). The kallikrein-kinin system as a mediator in vasogenic brain edema. Part 2: Studies on kinin formation in focal and perifocal brain tissue. J. Neurosurg. 61:97-106.
Rahman, M.M., Bhoola, K.D., Elson, C.J., Lemon, M., and Dieppe, P.A. (1995). Identification and functional importance in the synovial fluids of patients with rheumatoid, psoriatic, and osteoarthritis. Ann. Rheum. Dis. 54:345-350.
Raidoo, D.M., Ramsaroop, R., Naidoo, S., and Bhoola, K.D. (1996). Regional distribution of tissue kallikrein in human brain. Immunopharm. 32:39-47.
Raidoo, D. M., Ramchurren, N. Naidoo, Y., Naidoo, S., Muller-Esterl, W., and Bhoola, K.D. (1996). Visualisation of bradykinin B2 receptors on human brain neurons. Immunopharm. 33:104-107.
Raidoo, D.M., and Bhoola, K.D. (1997). Kinin receptors on human neurones. J. Neuroimmunol. 77:39-44.
Raidoo, D.M., (1999). Kinins in the human brain. University of Natal Nelson R. Mandela School of Medicine. Durban, S.A. PhD Thesis.
Regoli, D., and Barabé J. (1980). Pharmacology of bradykinin and related kinins. Pharmacol. Rev. 32:1-46.
Sambrook, J., Fritsch, E.F., and Maniatus, T. (1989). Molecular Cloning: a laboratory manual. (2ed) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. 18.12.
Schapira, M., Scott, C.F., and Colman, R.W. (1982). Contribution of plasma kallikrein protease inhibitors to the inactivation of kallikrein in plasma. J. Clin. Invest. 69:462-468.
Seidah, N.G., Paquin, J., Hamelin, J., Benjannet, S., and Chrétien, M. (1988). Structural and immunological homology of human and porcine pituitary and plasma IRCM-serine protease 1 to plasma kallikrein: marked selectivity for pairs of basic residues suggests a widespread role in pro-hormone and pro-enzyme processing. Biochemie 70:33-46.
Shcherbakova, I., Neshkova, E., Dotsenko, V., Platonova, T., Shcherbakova, E., and Yarovaya, G. (1999). The possible role of plasma kallikrein-kinin system and leukocyte elastase in pathogenesis of schizophrenia. Immunopharm. 43:273-279.
Takano, M., Horie, M., Narahara, M., Miyake, M., and Okamoto, H. (1999). Expression of kininogen mRNA by cultured neurons, astrocytes and meningeal cells in the rat brain. Immunopharm. 45:121-126.
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Cerf, M., Raidoo, D. Immunolocalization of Plasma Kallikrein in Human Brain. Metab Brain Dis 15, 315–323 (2000). https://doi.org/10.1023/A:1011179426420
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DOI: https://doi.org/10.1023/A:1011179426420