title: Technical advance: Inhibition of neutrophil chemotaxis by colchicine is modulated through viscoelastic properties of subcellular compartments.
abstract: Colchicine is an efficient drug for the management of inflammatory diseases, such as gouty arthritis and familial Mediterranean fever. It affects neutrophil activity by interfering with the formation of microtubules. To test the hypothesis that therapeutic concentrations of colchicine modulate the mechanical properties of these cells, we applied a combination of biophysical techniques (optical stretching and microrheology) to analyze cellular deformability. The contribution of the subcellular compartments to the regulation of cell mechanics was determined by fitting a multicomponent model of cellular viscoelasticity to time-dependent deformation curves. Neutrophils were found to be less deformable in response to 10 ng/ml colchicine. The model-based analysis of cellular deformation revealed a decrease in cytoplasmatic elasticity and a substantial increase in both elasticity and viscosity of the cell membrane compartment in response to colchicine. These results correlate with a reduced number of cytoplasmatic microtubules and an increase in subcortical actin filaments. The latter finding was confirmed by microrheology and fluorescence microscopy. Neutrophil migration through small pores requiring substantial cellular deformations, but not through large pores, was significantly impaired by colchicine. These data demonstrate that colchicine determines mechanics of neutrophils and, thereby, motility in confined spaces, which is crucial during extravasation of neutrophils in response to inflammatory stimuli.
authors.affiliation: 1.University of Ulm, 89081 Ulm, Germany. michael.beil@uni-ulm.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Paschke
authors.forename: Astrid Franziska
authors.initials: AF
authors.lastname: Weidner
authors.forename: Tobias
authors.initials: T
authors.lastname: Paust
authors.forename: Othmar
authors.initials: O
authors.lastname: Marti
authors.forename: Michael
authors.initials: M
authors.lastname: Beil
authors.forename: Eldad
authors.initials: E
authors.lastname: Ben-Chetrit
mesh_terms: D002462:Cell Membrane / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003078:Colchicine / Q000494:pharmacology*; D004548:Elasticity; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D014783:Viscosity
chemical_list: D003078:Colchicine
keywords: cellular deformability; cytoskeleton; extravasation; inflammation