A receptor for cathepsin G

Abstract

To determine whether there is a specific receptor for serpin:protease complexes on the astrocyte cell surface, we analyzed the cell-binding characteristics of an 125I-cathepsin G:α1antichymotrypsin complex. Complex formation is maximal at a 1:1 molar ratio of cathepsin G to α1-antichymotrypsin (α1-ACT) as revealed by sodium do-decyl sulfate-gel electrophoresis and autoradiography. Complex binding to mouse spinal cord astrocytes was inhibited by the presence of excess unlabeled complex, but not by the native protease, cathepsin G, or by the serpin, α1ACT. Scatchard analysis of the binding curve showed the Kd to be 8 × 10−8 M. We estimated receptor numbers on astrocytes to be about 2.2 × 106 sites per cell. An α-ACT-derived pentapeptide, Phe-Leu-Met-Ile-Ile (FLMII), homologous to a well-conserved segment in the serpin superfamily, did not inhibit the binding of complexes to cells. These data indicate that a specific receptor for α1-ACT:cathepsin G exists on the CNS glial cell surface. Study of this receptor in astrocytes should facilitate understanding of the serpin:protease balance in the brain.