| Autor: |
Schmausser, Bernd, Josenhans, Christine, Endrich, Simon, Suerbaum, Sebastian, Sitaru, Cassian, Andrulis, Mindaugas, Brändlein, Stephanie, Rieckmann, Peter, Müller-Hermelink, Hans Konrad, Eck, Matthias |
| Zdroj: |
Infection and Immunity; December 2004, Vol. 72 Issue: 12 p6773-6779, 7p |
| Abstrakt: |
ABSTRACTIn Helicobacter pylorigastritis, 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 Groα, 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. pylorihas not been investigated. Incubation of neutrophils with cag+and cagdeletion H. pyloristrains 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 cagstatus. 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. pylorilipopolysaccharide, 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. pyloristrains induced significantly stronger downregulation of CXCR1 and CXCR2 mRNAs than the cagdeletion 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. pyloriinfection. Downregulation of CXCR1 and CXCR2 expression on neutrophils in H. pyloriinfection by H. pyloriitself may represent a new mechanism of modulating neutrophil migration and activation in the gastric mucosa. |
| Databáze: |
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