Immunolocalization of plasma kallikrein in human brain.

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.