Activation of lysosomal enzymes in polymorphonuclear leukocytic granules: the role of phospholipid-protein interaction.

The concept of lysosomes as formulated in 1959 by DeDuve and hiis group(l) inclicates that the activation and release of lysosomal enzymes (lepends on the membrane surrounding lysosomes. If the lysosomal membrane is intact, lysosomal enzymes are bound and inactive. If the membrane becomes labilized or ruptured, lysosomal enzymes are free and active. It has been concluded that the stability of the lysosomal membrane dlepends on protein as well as lipid portions of the membrane. Lysosomal enzymes become active during phagocytosis and participate in the intracellular digestion of engulfed particles(2). Stuclh activation and release of lysosomal enzymes in plhagocytic cells is due to a fusion of the lysosomal membrane withi the membrane of a plhagocytic vacuole(3-5). In an attempt to elucidate a meclhanism underlying this process, we have previously demonstrated that model membranes (liposomes) composed of negatively clhargecl phosplholipids induce a similar effect upon leukocytic granules in a cell-free system(6,7). It lhas been suggested that the activating effect of phospholipid model membranes on granulocytic lysosomes may be mediated by a phospholipid-protein interaction. This possibility prompted us to define tlle component of granules whiclh interacts with phosplholipids. Leukocytic granules possess a class of arginine-rich cationic proteins which do not exhibit activity of lysosomal marker enzymes and which may be obtained from granules by acid extrac