Additive effects of Helicobacter pylori lipopolysaccharide and proteins in monocyte inflammatory responses

Background: Chronic active gastritis associated with Helicobacter pylori infection is characterized by both a neutrophil and a mononuclear leukocyte infiltrate. While neutrophil functions in relation to H. pylori are well described, the interactions between Helicobacter bacterial factors and monocytes are poorly understood in relation to the mucosal inflammatory process. Methods: Sonicates of a clinical strain as well as of a type strain of H. pylori were prepared in vitro. Monocytes from healthy donors were induced to release L-selectin (CD62L), to upregulate the adherence molecules (CD11a, CD11b, CD11c) and to produce toxic oxygen radicals. The inducing activities were assessed by flow cytometry and chemiluminescence. Results: A dose-dependent shedding of CD62L and upregulation of CD11b and CD11c were observed with both bacterial strains as well as PMA and fMLP. CD11a remained unchanged. Activity could be attributed to bacterial factors of both lipopolysaccharide (LPS) and protein characteristics. The alterations observed for CD11b, CD11c and CD62L were induced by the same protein fractions in parallel, suggesting a common component and mechanism of action. A major protein component was urease, although other minor protein bands were found as well. Monoclonal antibodies to CD14-inhibited monocyte inflammatory responses induced by H. pylori sonicate at low concentration, whereas further LPS pierce-matrix reduction was necessary at high sonicate concentrations to reduce monocyte-inducing activity. Conclusions: Monocyte inflammatory activation is induced by H. pylori sonicate components. Factors of both LPS and protein characteristics are involved and an additive effect was demonstrated. Urease appears to be a major component in the protein preparations of highest inducing capacity. Further studies are warranted to assess whether the monocyte activation properties described here are related to the diversity of clinical gastroduodenal outcome for the chronic type B gastritis associated with H. pylori infection.