Secretory Responses of Human Neutrophils: Exocytosis of Specific (Secondary) Granules by Human Neutrophils during Adherence in vitro and during Exudation in vivo

Abstract

Human neutrophils have been shown to release lysozyme spontaneously when incubated in vitro in the presence of physiologic concentrations of calcium. This spontaneous release of lysozyme, stored in both the azurophil and specific granules of neutrophils, reflects a selective mobilization and exocytosis of the specific granules, for it occurs without release of granule products located strictly in the azurophil granules (i.e., β-glucuronidase). Calcium-dependent lysozyme release without β-glucuronidase release by human neutrophils is significantly enhanced when the cells are exposed to surfaces to which they avidly adhere (nylon fibers and glass). Release of lysozyme, without a comparable release of β-glucuronidase, also occurs when human neutrophils migrate across cellulose nitrate micropore filters in vitro in response to a chemotactic stimulus. These phenomena in vitro appear to mimic events that occur in vivo when human neutrophils leave the circulation to become exudate cells. Specific granule products (lysozyme and B₁₂-binding protein) but not azurophil granule products appear in the extracellular fluid of experimental inflammatory lesions in vivo coincident with the influx of exudate neutrophils. Also, analysis of the granule content of exudate neutrophils, by granule separation techniques and by cytochemistry and electronmicroscopy, demonstrates a loss of specific granules but not azurophil granules from exudate cells when compared with peripheral blood neutrophils studied concurrently. Results of these studies support the concept that neutrophil-specific granules function in part like the storage granules of secretory cells and that mobilization and exocytosis of these granules by neutrophils are intrinsic to normal inflammatory responses. The release of specific granule products may contribute to extracellular killing or inhibition of microorganisms, but may also provide mechanisms by which neutrophils influence other inflammatory blood and tissue cells.