Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient.
Bottom Line: Neutrophils respond to invading bacteria by adopting a polarized morphology, migrating in the correct direction, and engulfing the bacteria.Attractant-induced activation of myosin phosphatase deactivated moesin at the prospective leading edge to break symmetry and establish polarity.Subsequent translocation of moesin to the trailing edge confined the formation of a prominent pseudopod directed toward pathogens and prevented secondary pseudopod formation in other directions.
Affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.Show MeSH
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Mentions: To address the role of moesin in neutrophil-mediated microbial killing and inflammation, we monitored the killing of bacteria in mouse lungs after inducing pneumonia using Pseudomonas aeruginosa strain 103 (PA103) through intratracheal (i.t.) injection. We observed an augmented load of P. aeruginosa in moesin knockout (Msn−/Y) lungs compared with WT lungs (Fig. 1 A; P < 0.01). Approximately 88% of the total 2 × 105 bacteria injected were killed in WT lungs, whereas only ∼26% were killed in Msn−/Y lungs (Fig. 1 B). To assess direct microbial killing by neutrophils, we isolated Msn−/Y neutrophils and performed bacterial killing in vitro. Compared with WT neutrophils, Msn−/Y neutrophils showed a significantly reduced microbial killing ability (Fig. 1 C; P < 0.01).
Affiliation: Department of Pharmacology and Department of Medicine, University of Illinois, Chicago, IL 60612.