Mobilization of gelatinase-rich granules as a regulatory mechanism of early functional responses in human neutrophils.

Components involved in superoxide anion production (cytochrome b) and in cell adhesion processes (CD11b, CD11c, CD18), two early functional responses of neutrophils during acute inflammation, are intracellularly located in resting human neutrophils. We have found a correlation between secretion of gelatinase and overexpression in the plasma membrane of CD11b, CD11c, CD18 and cytochrome b upon cell activation. Gelatinase and lactoferrin were parallely released after cell activation with different stimuli, but a better correlation between antigen up-regulation and gelatinase release was obtained. Total translocation of the intracellular pool of these mobilizable molecules to plasma membrane was achieved under conditions that induced total degranulation of the gelatinase-rich granule population, whereas 50% and 90% of the lactoferrin-containing secondary granules and peroxidase-containing primary granules, respectively, remained unfused. These results suggest a mechanism by which neutrophil function can be regulated through mobilization of gelatinase-rich granules, which can be considered as a subpopulation of secondary granules.