The experiments described in this proposal have been designed to elucidate the factors that regulate the selective release of lysosomal constituents from human polymorphonuclear leukocytes (PMN's). The applicant's previous studies of C5a-mediated lysosomal enzyme release from cytochalasin B-treated human PMN's will be expanded in an attempt to determine the roles of cyclic nucleotides, microtubule assembly, membrane fusion, energy metabolism and divalent cations in this phenomenon. The proposed studies will test the hypothesis that the usual shuttle and flow of lysosomes, and the recompartmentalization of their contents, may be regulated by a discrete series of events involving: a) perturbation of the plasma membrane, b) accumulation of either cAMP or cGMP: these either regulate the traffic of lysosomes or affect membranes directly, c) assembly or disassembly of cytoplasmic microtubules, and, finally d) the fusion of lysosomal membranes with phagocytic vacuoles and/or the plasma membrane. Specific attention will be focused on the role of calcium in facilitating or initiating these events, and on the recently observed phenomenon of lysozyme secretion from human PMN's that can be provoked by calcium, in the absence of other stimuli. BIBLIOGRAPHIC REFERENCES: Weissmann, G., Goldstein, I., Hoffstein, S.: Prostaglandins and the modulation by cyclic nucleotides of lysosomal enzyme release. Advances in Prostaglandin and Thromboxane Research, Vol. 2, (B. Samuelsson and R. Paoletti, Eds.) Raven Press, New York, pp. 803-814, 1976. Goldstein, I.M., Cerqueira, M., Lind, S., Kaplan, H.B.: Evidence that the superoxide generating system of human leukocytes is associated with the cell surface. Journal of Clinical Investigation 59:249-254, 1977.