Calcium Signaling in Migrating Neutrophils

Neutrophils are highly motile white blood cells that protect our body against bacterial and fungal infections. Local and global cytosolic Ca²⁺ elevations enhance the ability of neutrophils to phagocytose and kill microbes, but how Ca²⁺ signals regulate neutrophil adhesion, spreading, and <i>trans</i>-endothelial migration is unclear. Following the detection of chemotactic cues, selectin and integrin adhesion molecules unfold to interact with their ligands on the endothelial wall, triggering an extensive remodeling of the actin-based cytoskeleton that drives neutrophil migration and extravasation. Multiple intracellular signaling cascades are engaged by the activation of chemokine receptors, selectins, and integrins that coordinate actin-based motility and actin turnover to ensure the efficient directed migration of neutrophils to their targets. Here, we review how selectin and integrin-mediated Ca²⁺ elevations regulate neutrophil adhesion and spreading, the molecular and ultrastructural basis of localized Ca²⁺ signals in neutrophils, and the pathways decoding the Ca²⁺ signals that sustain actin-based neutrophil motility.