title: Neutrophil leukocyte motility requires directed water influx.
abstract: The ability of neutrophils to sense and move to sites of infection is essential for our defense against pathogens. For motility, lamellipodium extension and stabilization are prerequisites, but how cells form such membrane protrusions is still obscure. Using contrast-enhanced video microscopy and Transwell assays, we show that water-selective aquaporin channels regulate lamellipodium formation and neutrophil motility. Addition of anti-aquaporin-9 antibodies, HgCl(2), or tetraethyl ammonium inhibited the function(s) of the channels and blocked motility-related shape changes. On human neutrophils, aquaporin-9 preferentially localized to the cell edges, where N-formyl peptide receptors also accumulated, as assessed with fluorescence microscopy. To directly visualize water fluxes at cell edges, cells were loaded with high dilution-sensitive, self-quenching concentrations of fluorophore. In these cells, motile regions always displayed increased fluorescence compared with perinuclear regions. Our observations provide the first experimental support for motility models where water fluxes play a pivotal role in cell-volume increases accompanying membrane extensions.
authors.affiliation: Division of Medical Microbiology, Department of Health and Environment, Faculty of Health Sciences, Linköping University, Sweden. veslo@ihm.liu.se
authors.forename: Vesa-Matti
authors.initials: VM
authors.lastname: Loitto
authors.forename: Tony
authors.initials: T
authors.lastname: Forslund
authors.forename: Tommy
authors.initials: T
authors.lastname: Sundqvist
authors.forename: Karl-Eric
authors.initials: KE
authors.lastname: Magnusson
authors.forename: Mikael
authors.initials: M
authors.lastname: Gustafsson
mesh_terms: D020346:Aquaporins / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D022081:Cell Surface Extensions / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D014867:Water / Q000502:physiology
chemical_list: C109669:AQP9 protein, human; D020346:Aquaporins; D014867:Water