Mechanism of extracellular release of human neutrophil calprotectin complex

Calprotectin is an abundant cytosolic protein complex of human neutrophils with in vitro extracellular antimicrobial activity. Studies suggest that ca lprotectin may be actively secreted from intact HL-60 cells and that it can be translocated to polymorphonuclear neutrophil (PMN) cell membranes. To e xamine whether calprotectin is secreted extracellularly, we incubated solub le and particulate stimuli, including live and heat-inactivated Candida alb icans, with whole blood and measured calprotectin levels in the plasma. We compared the release of calprotectin to that of lactoferrin, a protein know n to be secreted by PMNs. Extracellular lactoferrin was detected after incu bation with any of the particulate stimuli. In contrast, a significant incr ease in extracellular calprotectin was found only after incubation with Liv e C. albicans, Specifically, the increase in extracellular calprotectin cor related directly with a proportional decrease in PMN viability. Our results indicate that human PMN calprotectin is not secreted extracellularly excep t as a result of cell disruption or death.