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Infection and Immunity, July 2003, p. 3724-3729, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.3724-3729.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Control of the Oxidative Burst of Human Neutrophils by Staphylococcal Leukotoxins

Didier A. Colin* and Henri Monteil

Laboratoire de Physiopathologie et d'Antibiologie des Infections Bactériennes Emergentes et Nosocomiales (UPRES-EA 3432), Institut de Bactériologie de la Faculté de Médecine, Université Louis Pasteur-Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France

Received 19 February 2003/ Returned for modification 21 March 2003/ Accepted 4 April 2003

The ability of staphylococcal two-component leukotoxins to induce an oxidative burst and/or to prime human polymorphonuclear cells (PMNs) was studied by using spectrofluorometry or flow cytometry. At sublytic concentrations, the HlgA-HlgB, HlgA-LukF-PV, LukS-PV-LukF-PV, and HlgC-LukF-PV combinations of leukotoxins, but not the LukS-PV-HlgB and HlgC-HlgB combinations, were able to induce H2O2 production similar to the H2O2 production induced by 1 µM N-formyl-Met-Leu-Phe (fMLP). In addition, when added at sublytic concentrations, all of the leukotoxin combinations primed PMNs for H2O2 production induced by fMLP. Leukotoxin activation was dependent on the presence of Ca2+ and was inhibited by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, but not by N-methyl-L-arginine, an inhibitor of NO generation, which eliminates the possibility that NO plays a role in the action of leukotoxins. At higher concentrations, all leukotoxins inhibited H2O2 production by PMNs activated by fMLP, phorbol 12-myristate 13-acetate (PMA), or the leukotoxins themselves. This inhibition was not related to the pore formation induced by leukotoxins. Intracellular release of H2O2 induced by fMLP and PMA was not primed by leukotoxins but was inhibited. It seems that leukotoxin inhibition of H2O2 release is independent of pore formation but secondary to an intracellular event, as yet unknown, triggered by leukotoxins.


* Corresponding author. Mailing address: LPAIBEN, Institut de Bactériologie, 3 rue Koeberlé, 67000 Strasbourg, France. Phone: 33 (0) 3 90 24 37 54. Fax: 33 (0) 3 88 25 11 13. E-mail: didier.colin{at}medecine.u-strasbg.fr.

Editor: J. T. Barbieri


Infection and Immunity, July 2003, p. 3724-3729, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.3724-3729.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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