The role of calcium in neutrophil granule-phagosome fusion

Abstract

During phagocytosis, neutrophils kill microorganisms by delivering antimicrobial substances to the phagosome. For this, the intracellular targeting and fusion of granules must be strictly regulated and a dependence on the cytosolic concentration of free calcium has been suggested. New evidence show that different mechanisms regulate early and late stages of Fc receptor-mediated phagocytosis. The early fusion events are dependent on calcium but this is not the case for the fusion of azurophilic granules with phagosomes at later stages. Certain pathogens target the granule-phagosome fusion machinery in order to survive intracellularly; a deeper understanding of intracellular membrane traffic processes could allow new approaches for the eradication of pathogens that are harbored inside the cells of our immune system.

Keywords: azurophilic granules; calcium; membrane fusion; membrane traffic; neutrophil; phagocytosis; phagosome.

Figure 1

The role of calcium in neutrophil granule-phagosome fusion. During Fc-receptor-mediated phagocytosis, tyrosine residues on the receptors are phosphorylated and trigger a signaling cascade. Granules are delivered and fuse with the plasma membrane in a calcium-dependent manner already before the phagosome is sealed. The trafficking of azurophilic granules is guided by microtubules, originating from the microtubule-organizing center that re-locates to the site of phagocytosis. Once the phagosome is formed, delivery and fusion of granules continue by unknown calciumindependent mechanisms.