Protein synthesis-dependent and protein synthesis-independent secretion of lysosomal hydrolases from rabbit and human macrophages.

Rabbit alveolar macrophages and human monocyte-derived macrophages released lysosomal enzymes in response to a variety of stimuli. The release of these enzyme appeared to be under the control of at least two distinct mechanisms. The first involved a rapid release of preformed granule constituents in response to a phagocytic load. This release reaction was concentration- and time-dependent, was not affected by the protein synthesis inhibitors cycloheximide and puromycin, and resulted in a concomitant loss in intracellular enzyme levels. The second mechanism involved a prolonged secretion in response to lower concentration of stimuli, which increased with time, and was inhibited by cycloheximide and puromycin. The secretion did not result in the loss of intracellular enzyme stores; rather an induction of enzyme was seen following such stimulation, which resulted in increases in the total concentration within the cultures. This protein synthesis-dependent secretion of acid hydrolases from human macrophages varied for each lysosomal hydrolase and each stimulus. beta-Glucosaminidase synthesis and secretion was induced by low-dose opsonized zymosan, by latex particles, and by formaldehyde-treated SRBC. However, only the last mentioned stimulus caused release of acid phosphates although all three particles induced synthesis of the enzyme. None of the stimuli at these concentrations (10:1 particle to cell ratio) caused the release of beta-glucoronidase, although the enzyme was releasable if higher stimulus concentrations were used. In addition the enzyme was not inducible under these conditions. It is concluded that each of the acid hydrolases studied may be under different control in the human macrophage and that the cells may respond in a qualitatively different way to different types of phagocytosable stimuli.