Immunolocalization of plasma kallikrein in human brain

Plasma kallikrein (PK) is a cofactor in blood coagulation and modulates inf lammation through the release of bradykinin. Previously it was believed tha t plasma prekallikrein (PPK), the precursor of PK and a member of the serin e protease superfamily, was synthesized exclusively by hepatocytes and secr eted into circulation. However, recent studies show that the human brain co ntains 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 differen t regions of the human brain were collected at autopsy within 24h from deat h. Sections were probed using polyclonal antibodies (characterized by Weste rn blotting) specific for PK. PK concentrations in extracts of these tissue s were measured by ELISA. Immunolabeling of PK was observed in the cell bod ies of the neurons of the hypothalamus, thalamus, spinal cord, cerebral cor tex and brainstem. Positive PK immuno-reactivity was also demonstrated in t he cytoplasm of the ependymal cells in sections of the hypothalamus and spi nal cord. In addition, some fibre tracts of the pens, medulla and hippocamp us as well as secretory cells of the pituitary gland also labeled. No immun oreactive PK was visualized in the choroid plexus or cerebellum. Our data d emonstrate the cellular localization of PK in human brain. This work is sup ported by other studies that demonstrate PK mRNA in human heart, lung, trac hea and brain. The cellular distribution of PK and kinin receptors in speci fic brain areas suggests a role for PK in the nervous system.