The secretion of lysosomal enzymes

The studies reviewed in this chapter provide further evidence that the secretion of lysosomal enzymes and other hydrolases is a constitutive function of certain cells whereas in other cells is an inducible process probably contributing to the pathology of a variety of diseases. Little is known of the mechanisms mediating the secretion of lysosomal enzymes. We have summarized evidence suggesting a role of microfilaments and microtubules in controlling enzyme release, but further studies of the biochemical mechanisms which control the activity of these subcellular structures are required. The fusion of lysosomes with the plasma membrane has been observed in several situations and the mechanisms underlying processes of this nature have been studied in lower organisms (Satir et al. 1973; Plattner 1974). Agents, such as concanavalin A, which interfere with the fusion of endosomes with lysosomes (Goldman 1974; Edelson and Cohn 1974a, b) should also be useful in determining the chemical nature of membrane components involved in the fusion process. New information on the fate of secreted acid hydrolases has been obtained from studies of the uptake of lysosomal enzymes by fibroblasts. Clearly, the mechanisms by which these cells endocytose secreted lysosomal enzymes will be a subject for detailed study in view of the important of directing enzymes and drugs into lysosomes (De Duve et al. 1974). The mechanisms by which extracellular inhibitors inactivate hydrolytic enzymes, particularly proteinases, is also being clarified (for review see Davies 1975) and this should aid in finding new ways for preventing tissue damage caused by the excessive secretion of these enzymes. Further investigation concerning the secretion of lysosomal enzymes should establish the essential physiological role which these enzymes play at both extracellular and intracellular sites. Also, a close examination of the interaction of both endogenous and exogenous stimuli of inflammation with cells resulting in the secretion of hydrolytic enzymes, will clarify the mechanisms underlying the initiation and progression of the inflammatory process in its diverse forms.