Polarization and directed migration of murine neutrophils is dependent on cell surface expression of CD44

The importance of CD44 in murine neutrophil chemotaxis was studied in a Zigmond chamber. WT neutrophils polarized more rapidly and more extensively than CD44−/− neutrophils, which showed slow random migration and reduced activation of RhoA. CD44+/− neutrophils polarized more slowly, formed fewer directionally polarized cells, and migrated more slowly than WT cells. Antibodies to CD44 decreased polarization of WT neutrophils and reduced directed migration but not migration speed, indicating that CD44 mediates chemotactic signaling and migration through different pathways, while a hyaluronate substratum markedly reduced both the speed and directed migration of WT cells. In contrast to macrophages, the level of cell surface CD44 in neutrophils was not affected by osteopontin expression and CD44 did not co-localize with osteopontin. In polarized neutrophils, CD44 was enriched in uropods while cortical actin was predominant at the leading edge. Thus, both polarization and directed migration of neutrophils are dependent on the expression of CD44 and its interaction with hyaluronan, which could modulate neutrophil migration into inflamed tissues.