The secretion of preformed granules by macrophages and neutrophils

The ability of macrophages and neutrophils to defend tissue homeostasis and participate in inflammatory responses depends on their ability to mobilize granule-membrane proteins and granule content into their external milieu and into phagosomes by regulated secretory processes. Many laboratories have invested much time and effort into furthering our understanding of vesicular transport and secretion. A surge of interest in phagocytosis and phagosomal maturation is also apparent (e.g., the March 1995 issue of Trends in Cell Biology was entirely devoted to phagocytosis). The signaling and the regulation of the secretory response are most likely different for secretion into phagosomes than for secretion into the external milieu. However, these differentially targeted secretory processes rely both upon proteins in vesicular membranes, plasma membrane/phagosomal membrane, and cytosol and upon their interactions with cytoskeletal structures. It is the complex molecular interactions between these components that form the basis for regulation and control of secretion. In the following, the signaling role of granular and cytosolic pH in phagocyte lysosomal secretion is discussed and the current literature on regulated secretion by macrophages and neutrophils is reviewed.