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Aerolysin induces G-protein activation and Ca2+ release from intracellular stores in human granulocytes

Fivaz, M.
van der Goot, F. G.
Published in Journal of Biological Chemistry. 1998, vol. 273, no. 29, p. 18122-18129
Abstract Aerolysin is a pore-forming toxin that plays a key role in the pathogenesis of Aeromonas hydrophila infections. In this study, we have analyzed the effect of aerolysin on human granulocytes (HL-60 cells). Proaerolysin could bind to these cells, was processed into active aerolysin, and led to membrane depolarization, indicating that granulocytes are potential targets for this toxin. Fura-2 measurements were used to analyze the effect of aerolysin on cytosolic [Ca2+] homeostasis. As expected for a pore-forming toxin, aerolysin addition led to Ca2+ influx across the plasma membrane. In addition, the toxin triggered Ca2+ release from agonist and thapsigargin-sensitive intracellular Ca2+ stores. This Ca2+ release was independent of the aerolysin-induced Ca2+ influx and occurred in two kinetically distinct phases: an initial rapid and transient phase and a second, more sustained, phase. The first, but not the second phase was sensitive to pertussis toxin. Activation of pertussis toxin-sensitive G-proteins appeared to be a consequence of pore formation, rather than receptor activation through aerolysin-binding, as it: (i) was not observed with a binding competent, insertion-incompetent aerolysin mutant, (ii) had a marked lag time, and (iii) was also observed in response to other bacterial pore-forming toxins (staphylococcal alpha-toxin, streptolysin O) which are thought to bind to different receptors. G-protein activation through pore-forming toxins stimulated cellular functions, as evidenced by pertussis toxin-sensitive chemotaxis. Our results demonstrate that granulocytes are potential target cells for aerolysin and that in these cells, Ca2+ signaling in response to a pore-forming toxin involves G-protein-dependent cell activation and Ca2+ release from intracellular stores.
Keywords Bacterial ProteinsBacterial Toxins/metabolism/ pharmacologyCalcium/ metabolismCell Membrane Permeability/drug effectsChemotaxis, Leukocyte/drug effectsDigitonin/pharmacologyGTP-Binding Proteins/ metabolismGranulocytes/drug effects/ metabolismHL-60 CellsHemolysin Proteins/metabolism/ pharmacologyHumansIon Channels/ metabolismKineticsMembrane PotentialsN-Formylmethionine Leucyl-Phenylalanine/pharmacologyPertussis ToxinPore Forming Cytotoxic ProteinsPotassium/metabolismStreptolysins/metabolismVirulence Factors, Bordetella/pharmacology
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PMID: 9660770
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