title: Calcium flux in neutrophils synchronizes beta2 integrin adhesive and signaling events that guide inflammatory recruitment.
abstract: Intracellular calcium flux is an early step in the signaling cascade that bridges ligation of selectin and chemokine receptors to activation of adhesive and motile functions during recruitment on inflamed endothelium. Calcium flux was imaged in real time and provided a means of correlating signaling events in neutrophils rolling on E-selectin and stimulated by chemokine in a microfluidic chamber. Integrin dependent neutrophil arrest was triggered by E-selectin tethering and ligation of IL-8 seconds before a rapid rise in intracellular calcium, which was followed by the onset of pseudopod formation. Calcium flux on rolling neutrophils increased in a shear dependent manner, and served to link integrin adhesion and signaling of cytoskeletally driven cell polarization. Abolishing calcium influx through membrane expressed store operated calcium channels inhibited activation of high affinity beta(2) integrin and subsequent cell arrest. We conclude that calcium influx at the plasma membrane integrates chemotactic and adhesive signals, and functions to synchronize signaling of neutrophil arrest and migration in a shear stress dependent manner.
authors.affiliation: Department of Biomedical Engineering, Genome and Biomedical Sciences Facility, University of California, Davis, 451 E. Health Sciences Dr., Davis, CA 95616-5294, USA.
authors.forename: Ulrich Y
authors.initials: UY
authors.lastname: Schaff
authors.forename: Itsukyo
authors.initials: I
authors.lastname: Yamayoshi
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tse
authors.forename: Donald
authors.initials: D
authors.lastname: Griffin
authors.forename: Lilian
authors.initials: L
authors.lastname: Kibathi
authors.forename: Scott I
authors.initials: SI
authors.lastname: Simon
mesh_terms: D018821:CD18 Antigens / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002448:Cell Adhesion; D002478:Cells, Cultured; D006801:Humans; D040542:Mechanotransduction, Cellular; D018375:Neutrophil Activation; D009504:Neutrophils; D014657:Vasculitis / Q000503:physiopathology*
chemical_list: D018821:CD18 Antigens; D002118:Calcium