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Infection and Immunity, December 2004, p. 6773-6779, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6773-6779.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Downregulation of CXCR1 and CXCR2 Expression on Human Neutrophils by Helicobacter pylori: a New Pathomechanism in H. pylori Infection?

Bernd Schmausser,^1* Christine Josenhans,^2, Simon Endrich,¹ Sebastian Suerbaum,^2, Cassian Sitaru,³ Mindaugas Andrulis,¹ Stephanie Brändlein,¹ Peter Rieckmann,⁴ Hans Konrad Müller-Hermelink,¹ and Matthias Eck¹

Institut für Pathologie der Universität Würzburg,¹ Institut für Hygiene und Mikrobiologie,² Universitäts-Hautklinik,³ Neurologische Universitätsklinik, Universität Würzburg, Würzburg, Germany⁴

Received 1 March 2004/ Returned for modification 31 March 2004/ Accepted 12 August 2004

In Helicobacter pylori gastritis, neutrophil activation and migration, which play central roles in the pathogenesis of the disease, are regulated by the neutrophil attractant chemokines interleukin 8 (IL-8) and Gro, whose secretion is induced by H. pylori. However, the modulation of the corresponding chemokine receptors CXCR1 and CXCR2 on human neutrophils under the influence of H. pylori has not been investigated. Incubation of neutrophils with cag⁺ and cag deletion H. pylori strains resulted in a complete downregulation of the CXCR1 and the CXCR2 receptors after 0.5 h, as tested by fluorescence-activated cell sorter analysis, independent of the cag status. Downregulation of CXCR1 and CXCR2 seems to occur via receptor internalization and rapid degradation, as shown by confocal microscopy and immunoblotting. Neither the proinflammatory cytokines IL-8 and tumor necrosis factor alpha produced by the neutrophils themselves nor H. pylori lipopolysaccharide, which are the known regulators of these two chemokine receptors, was responsible for the downregulation. Reverse transcription-PCR analysis showed that CXCR1 and CXCR2 mRNAs of neutrophils were reduced at a later time than the CXCR1 and CXCR2 proteins. Moreover, cag⁺ H. pylori strains induced significantly stronger downregulation of CXCR1 and CXCR2 mRNAs than the cag deletion mutant. Therefore, receptor protein and mRNA downregulation seem to be mediated by two independent mechanisms. Data obtained by immunohistochemistry suggested that downmodulation of CXCR1 and CXCR2 on neutrophils may also occur in vivo in the human stomach during H. pylori infection. Downregulation of CXCR1 and CXCR2 expression on neutrophils in H. pylori infection by H. pylori itself may represent a new mechanism of modulating neutrophil migration and activation in the gastric mucosa.

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* Corresponding author. Mailing address: Institut für Pathologie, Universität Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany. Phone: 0049-(0)931-201-47778. Fax: 0049-(0)931-201-47440. E-mail: schmausser{at}web.de.

Editor: J. D. Clements

Present address: Medizinische Hochschule Hannover, Institut für Mikrobiologie und Krankenhaushygiene, Hannover, Germany.

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Infection and Immunity, December 2004, p. 6773-6779, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6773-6779.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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