The ability of macrophages and neutrophils to defend tissue homeostasi
s and participate in inflammatory responses depends on their ability t
o mobilize granule-membrane proteins and granule content into their ex
ternal milieu and into phagosomes by regulated secretory processes, Ma
ny laboratories have invested much time and effort into furthering our
understanding of vesicular transport and secretion, A surge of intere
st in phagocytosis and phagosomal maturation is also apparent (e.g., t
he March 1995 issue of Trends in Cell Biology was entirely devoted to
phagocytosis). The signaling and the regulation of the secretory respo
nse are most likely different for secretion into phagosomes than for s
ecretion into the external milieu, However, these differentially targe
ted secretory processes rely both upon proteins in vesicular membranes
, plasma membrane/phagosomal membrane, and cytosol and upon their inte
ractions with cytoskeletal structures, It is the complex molecular int
eractions between these components that form the basis for regulation
and control of secretion, In the following, the signaling role of gran
ular and cytosolic pH in phagocyte lysosomal secretion is discussed an
d the current literature on regulated secretion by macrophages and neu
trophils is reviewed.