Interaction of Factor XII and high molecular weight kininogen with cytokeratin 1 and gC1qR of vascular endothelial cells and with aggregated A beta protein of Alzheimer' s disease

High molecular weight kininogen (HK) attaches to endothelial cells at separ ate sites on the heavy and light chains by a process which requires 15-50 m u M zinc. Previously identified binding proteins include gClqR, cytokeratin 1, and the urokinase plasminogen activator receptor (U-par), however, thei r relative contribution to binding are not yet clarified. We have purified the binding proteins by affinity chromatography, in the presence of zinc io n, and identified cytokeratin 1 and gClqR by amino acid sequencing of an in ternal peptide and by immunoblot as heavy chain and light chain binding pro teins, respectively. Antibody to cytokeratin 1 inhibited HK binding to endo thelial cells by 30%, antibody to gClqR 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 Alzheim er's disease. Activation of the cascade using purified proteins or upon add ition 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. T he data demonstrate that aggregated AP can bind and activate proenzymes of the plasma kinin-forming cascade to release bradykinin and these reactions are dependent on zinc ion. (C) 1999 Elsevier Science B.V. All rights reserv ed.