REGULATION OF NEUTROPHIL MOTILITY AND ADHESION BY INTRACELLULAR CALCIUM TRANSIENTS

Neutrophils are guided lo the sites of infection or inflammation by gr adients of chemoattractants. Chemoattractants stimulate rapid and repe ated changes in neutrophil intracellular calcium, [Ca2+]i, which corre late with cell spreading, pseudopod extension, motility, change of dir ection and phagocytosis. However, blocking the [Ca2+]i transients has little effect on cell spreading, polarization or pseudopod extension. Thus, either the [Ca2+]i transients are not required for cell spreadin g, polarization or pseudopod extension or other redundant mechanisms a re present that allow the cells to perform these functions in vitro. I n contrast, cell motility is [Ca2+]i dependent when the cells are exam ined on physiological substrates such as fibronectin or vitronectin. C alcium-buffered cells appear to make repeated attempts to move but are unable to detach from a fibronectin or vitronectin substrate. Motilit y can be restored to [Ca2+]i buffered cells by blocking substrate atta chment with RGD peptides or by using a less adherent substrate such as albumin. A similar inhibition of motility on vitronectin could be ind uced by ihibitors of the calcium/calmodulin-dependent phosphatase, cal cineurin. Thus, the periodic increases in [Ca2+]i apparently activate the phosphatase calcineurin to initiate a cycle of detachment from the vitronectin substratum. These data suggest that the [Ca2+]i transient s regulate motility by coordinating a series of substrate-specific att achment/detachment events.