Aerolysin Induces G-protein Activation and Ca2+Release from Intracellular Stores in Human Granulocytes
| Autor: | Antoinette Monod, Karl-Heinz Krause, Marc Fivaz, F. G. van der Goot |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Calcium/ metabolism
Cell Membrane Permeability Pertussis Toxins/pharmacology Hemolysin Proteins/metabolism/ pharmacology Leukocyte/drug effects ddc:616.07 Digitonin/pharmacology medicine.disease_cause Biochemistry Ion Channels Membrane Potentials Hemolysin Proteins Virulence Factors Bordetella Granulocytes/drug effects/ metabolism Chemotaxis Calcium/*metabolism Cell biology N-Formylmethionine Leucyl-Phenylalanine Chemotaxis Leukocyte Ion Channels/*metabolism Aeromonas hydrophila GTP-Binding Proteins/ metabolism Streptolysins Support Chemotaxis Leukocyte/drug effects Cell activation Ion Channels/ metabolism Intracellular Human Pore Forming Cytotoxic Proteins Cell Membrane Permeability/drug effects G protein Granulocytes/drug effects/*metabolism Bacterial Toxins Potassium/metabolism Non-P.H.S Aerolysin Digitonin HL-60 Cells Biology Bacterial Toxins/metabolism/*pharmacology Pertussis toxin Bacterial Proteins GTP-Binding Proteins Streptolysins/metabolism medicine Humans Molecular Biology Bacterial Toxins/metabolism/ pharmacology Toxin G-Proteins/*metabolism Virulence Factors Bordetella/pharmacology Cell Biology Hemolysins/metabolism/*pharmacology biology.organism_classification Kinetics Pertussis Toxin Potassium Calcium U.S. Gov't N-Formylmethionine Leucyl-Phenylalanine/pharmacology Granulocytes |
| Zdroj: | Journal of Biological Chemistry, Vol. 273, No 29 (1998) pp. 18122-18129 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.273.29.18122 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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