A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis
Åsa Betten, … , Kristoffer Hellstrand, Claes Dahlgren
Åsa Betten, … , Kristoffer Hellstrand, Claes Dahlgren
Published October 15, 2001
Citation Information: J Clin Invest. 2001;108(8):1221-1228. https://doi.org/10.1172/JCI13430.
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Article

A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis

Abstract

Infection with Helicobacter pylori causes chronic gastritis, which is characterized by a dense mucosal infiltration by inflammatory cells such as monocytes/macrophages. H. pylori–induced inflammation is a risk factor for the development of gastric adenocarcinoma, but the mechanisms involved in H. pylori–associated carcinogenesis are poorly understood. A cecropin-like H. pylori peptide, Hp(2-20), was found to be a monocyte chemoattractant and activated the monocyte NADPH-oxidase to produce oxygen radicals. The receptors mediating monocyte activation were identified as FPRL1 and the monocyte-specific orphan receptor FPRL2. Hp(2-20)–activated monocytes inhibited lymphocytes with antitumor properties, such as CD56+ natural killer (NK) cells and CD3ε+ T cells. The changes observed in NK cells and T cells — a reduced antitumor cytotoxicity, downregulation of CD3ζ expression, and apoptosis — were mediated by Hp(2-20)–induced oxygen radicals. Histamine, a gastric mucosal constituent, rescued NK cells and T cells from inhibition and apoptosis by suppressing Hp(2-20)–induced oxygen radical formation. We conclude that H. pylori expression of this monocyte-activating peptide contributes to its ability to attract and activate monocytes and reduces the function and viability of antineoplastic lymphocytes. These novel mechanisms may be subject to local, histaminergic regulation in the gastric mucosa.

Authors

Åsa Betten, Johan Bylund, Thierry Cristophe, François Boulay, Ana Romero, Kristoffer Hellstrand, Claes Dahlgren

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Hp(2–20)–induced monocyte chemotaxis and activation of the monocyte NADP...
Hp(2–20)–induced monocyte chemotaxis and activation of the monocyte NADPH-oxidase. Monocyte transmigration after 90 minutes in response to different Hp(2–20) concentrations was determined using a ChemoTx multiwell chamber system. Migration was determined microscopically by counting cells in the lower compartments. (a) Hp(2–20) induced chemotaxis in human monocytes in a dose-dependent manner. Mean values ± SEM of three separate experiments. Hp(2–20) (50 μM), but not the control peptide Hp1 (50 μM), triggered superoxide anion production in monocytes (b) with kinetics similar to that induced by the formylated peptide fMLF (inset). The Hp(2–20)–induced superoxide anion release was dose-dependent within the micromolar range (c). One representative experiment out of five (b and inset), and mean values ± SEM of five separate experiments (c).