Rapid biogenesis and sensitization of secretory lysosomes in NK cells mediated by target-cell recognition

Natural killer (NK) cells play important roles in defense against tumor, viral infection, and cell-mediated xenograft rejection through secretion of secretory lysosomes. In this study, we used high time-resolution membrane capacitance measurement and fluorescence-imaging techniques to study the biogenesis and exocytosis of secretory lysosomes in a human NK cell line. We demonstrated a high-affinity Ca2+-dependent exocytosis of secretory lysosomes, which is sensitized further after target-cell stimulation. Our data also suggest an unusual rapid and dramatic de novo formation of secretory lysosomes after target-cell recognition. The rapid biogenesis of secretory lysosomes was blocked by specific protein kinase C inhibitor but not by brefeldin A. We propose that target-cell recognition triggers rapid biogenesis and sensitization of secretory lysosomes in NK cells through activation of PKC.