title: Hg2+ and small-sized polyethylene glycols have inverse effects on membrane permeability, while both impair neutrophil cell motility.
abstract: Toxic effects after exposure to mercury are well documented in human. Little is, however, known about how Hg(2+) affect host defense in general and neutrophil functions in particular. We show here that exposure of human neutrophils to HgCl(2) dose-dependently impairs chemoattractant-stimulated motility. Long-term exposure (5-10 min) to Hg(2+) yields a rapid influx of extracellular Ca(2+) followed by leakage of cytosolic fluorophores, as assessed using fura-2 and ratio imaging microscopy. The inhibition on motility was partly reversible, since pre-treated neutrophils placed in an Hg(2+)-free environment displayed higher migration rates. The Hg(2+)-induced fluxes were prevented by addition of small-sized polyethylene glycols (PEG 200-400), which also dose-dependently inhibited neutrophil transmigration. Localized, minute micropipette additions of Hg(2+) or PEG caused retraction of the leading edge and redirection of cell migration. Since Hg(2+) increases and PEGs decrease membrane permeability in a partially competitive manner, we suggest that the known aquaporin-inhibitor Hg(2+) alters membrane permeability by affecting the bidirectional flux through the leukocyte aquaporin-9 (AQP9) while small-sized PEGs yield decreased membrane permeability by becoming trapped in the promiscuous channel. The local additions of Hg(2+) or PEG probably force other cell regions to take over from those with blocked AQPs. Hence, the cells turn direction of motility away from the micromanipulator needle.
authors.affiliation: Division of Medical Microbiology, Department of Molecular and Clinical, Medicine, Linköping University, SE-581 85 Linköping, Sweden. veslo@imk.liu.se
authors.forename: Vesa-Matti
authors.initials: VM
authors.lastname: Loitto
authors.forename: Karl-Eric
authors.initials: KE
authors.lastname: Magnusson
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D020346:Aquaporins / Q000037:antagonists & inhibitors / Q000276:immunology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000276:immunology; D008628:Mercury / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C109669:AQP9 protein, human; D000906:Antibodies; D020346:Aquaporins; D007473:Ion Channels; D011092:Polyethylene Glycols; D008628:Mercury