CALRETICULIN IS RELEASED FROM ACTIVATED NEUTROPHILS AND BINDS TO C1Q AND MANNAN-BINDING PROTEIN

The Ca2+ storage protein calreticulin is associated with the endoplasm ic reticulum and shares a high degree of amino acid homology with the surface receptor C1q-R. In this study, flow cytometric analysis detect ed calreticulin on the neutrophil surface, which decreased during stim ulation probably as a consequence of shedding, as calreticulin was fou nd by ELISA in the cell supernatants of stimulated cells. Antibodies r aised against C1q-R and calreticulin demonstrated a high degree of imm unological cross-reactivity for purified calreticulin as determined by dot blot analysis. Western blots of neutrophil subcellular fractions located calreticulin in both the cytosol and cell membrane fractions; C1q-R was largely confined to the cell membrane. Calreticulin and C1q- R both bind to C1q and mannan-binding protein. Therefore, calreticulin may be shed on cell activation and may be associated with the cell me mbrane, where it can potentially interact with C1q and serum lectins. The implications of this are discussed. (C) 1994 Academic Press, Inc.