Interaction of Factor XII and high molecular weight kininogen with cytokeratin 1 and gClqR of vascular endothelial cells and with aggregated A beta protein of Alzheimer's disease

• Published in: Immunopharmacology 1999-01, Vol.43 (2-3), p.203-210
• Main Authors: Joseph, K, Shibayama, Yoji, Nakazawa, Yoshitaka, Peerschke, EIB, Ghebrehiwet, B, Kaplan, AP
• Format: Article
• Language: English
• Subjects: Ab protein; complement component Clq; cytokeratin 1; kininogen
• ISSN: 0162-3109

High molecular weight kininogen (HK) attaches to endothelial cells at separate sites on the heavy and light chains by a process which requires 15-50 mu M zinc. Previously identified binding proteins include gC1qR, cytokeratin 1, and the urokinase plasminogen activator receptor (U-par), however, their relative contribution to binding are not yet clarified. We have purified the binding proteins by affinity chromatography, in the presence of zinc ion, and identified cytokeratin 1 and gC1qR by amino acid sequencing of an internal peptide and by immunoblot as heavy chain and light chain binding proteins, respectively. Antibody to cytokeratin 1 inhibited HK binding to endothelial cells by 30%, antibody to gC1qR inhibited HK binding to endothelial cells by 72%, and a mixture of both inhibited binding by 86%. The binding and activation of the proteins of the kinin-forming cascade along the cell surface is zinc-dependent. Similarly, proteins of the plasma kinin-forming cascade can be activated by binding to aggregated A beta protein of Alzheimer's disease. Activation of the cascade using purified proteins or upon addition of A beta to plasma requires aggregation of A beta and the reactions are zinc-dependent. In plasma, HK is cleaved and bradykinin is liberated. The data demonstrate that aggregated A beta can bind and activate proenzymes of the plasma kinin-forming cascade to release bradykinin and these reactions are dependent on zinc ion.