page 181, Dewitt and Hallett report that neutrophils need integrins and a Ca2+ boost to build a mouth that is up to the task.
Phagocytosis around a particle occurs in a series of steps that includes pseudopodial formation of a phagocytic cup and cup closure/retraction. When microbes present complement components, which are the targets for integrin binding, the phagocytic cups close around the bugs more rapidly. The authors found that this speediness correlated with a sequence of Ca2+ changes during both cup formation and closure. At cup formation, complement binding to integrin initiated the release of local Ca2+ stores near the contact site. Local increase caused an unknown PI3K- dependent signal to launch a cell-wide influx of Ca2+ just before particle enclosure. Although Hallett speculates that a locally activated phospholipid could stimulate Ca2+ channels as it diffuses around the plasma membrane, he admits that diffusion of the PI3K product, PIP3, is probably too slow to account for the rapid Ca2+ influx.
Global Ca2+ changes effected the rapid engulfment of tagged particles by releasing integrin receptors throughout the cell membrane. These receptors were then free to diffuse to the phagocytic site, where they could help hasten cup closure. Since calpain inhibitors blocked integrin diffusion and rapid phagocytosis, the authors conclude that Ca2+ may stimulate calpain protease activity throughout the cell. Calpain could cleave talin or some other, perhaps neutrophil-specific, protein that links integrin to the actin cytoskeleton. ▪