Effects of serum and cations on the selective release of granular proteins from human netrophils during phagocytosis

The extracellular release from human neutrophils of the primary (azurophil) granule constituents, myeloperoxidase (MPO), chymotrypsin-like cationic protein (CCP), collagenase and lysozyme, and the secondary (specific) granule constituents, lactoferrin and lysozyme, was measured during ingestion of staphylococcus protein-A-IgG complexes. In buffer, lactoferrin release was consistently higher than that of the other protein. In serum, lactoferrin release increased concomitantly with ingestion, whereas the rate of lysozyme and especially of MPO release were stimulated to a higher degree than ingestion. Magnesium (0.5--2 mM) was more potent than calcium (0.5--2 mM) in promoting release but these cations worked synergistically. Zinc (0.5--4 mM) was found to be a potent and selective inhibitor of collagenase release. Manganese (0.25--4 mM), which inhibited the ingestion of SpA-IgG complexes, also inhibited release of CCP, collagenase, lysozyme and MPO, but actually stimulated lactoferrin release. The data suggests that lactoferrin and lysozyme may be confined to distinct granule populations or else released in a different fashion from the granules. When the effects on release of primary granule proteins are concerned it is suggested that the dissociation of binding of various agents to an anionic granule matrix may be affected differently by various cations.