Neutrophil granule constituents and their release in health and disease

In this review of secretion by neutrophils, we have given a detailed description of the characteristics of the exocytotic responses of these cells to a variety of stimuli. Secretion of the contents of the two types of granules follows different rules. Azurophil granules are discharged only when neutrophils interact with phagocytizable particles, whereas specific granules are discharged on interaction of the cells with both particulate and soluble stimuli. In the latter case, specific granule constituents are released directly into the extracellular environment, demonstrating that these granules can function as secretory organelles. Studies of patients with specific granule deficiency have indicated the role of specific granules in modulating the inflammatory response. Additionally, studies of one of these patients has provided a better understanding of basic processes and pathways contributing to priming of neutrophils for subsequent activation by soluble stimuli. It appears that elevated intracellular calcium levels, rather than the mere translocation of protein kinase C to the plasma membrane, can account for the exaggerated response of specific granule-deficient cells to subsequent stimulation. Further studies are needed to unravel the biochemical mechanisms underlying the abnormal fusion of granules in the Chédiak-Higashi syndrome. It is possible that further studies of Chédiak-Higashi syndrome will result in a better understanding of the mechanisms by which granules normally fuse with phagosomes. Studies of the biochemical properties of novel secretory organelles containing either gelatinase or alkaline phosphatase and of their discharge on stimulation will also provide much needed information on the role of secretory events in the early stages of neutrophil adhesion, diapedesis, and movement within tissues.