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Helicobacter pylori lipopolysaccharide binds to CD14 and stimulates release of interleukin-8, epithelial neutrophil-activating peptide 78, and monocyte chemotactic protein 1 by human monocytes. 1998

C M Bliss, and D T Golenbock, and S Keates, and J K Linevsky, and C P Kelly
Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

Helicobacter pylori gastritis is characterized by leukocyte infiltration of the gastric mucosa. The aims of this study were to determine whether H. pylori-derived factors stimulate chemokine release from human monocytes and to ascertain whether H. pylori lipopolysaccharide (LPS) may be responsible for this effect. Human peripheral blood monocytes were exposed to an H. pylori water extract (HPE) or to purified H. pylori LPS. Levels of the chemokines interleukin-8 (IL-8), epithelial neutrophil-activating peptide 78 (ENA-78), and monocyte chemotactic protein 1 (MCP-1) were measured by enzyme-linked immunosorbent assay. The contribution of H. pylori LPS to monocyte activation was determined by using the LPS antagonist Rhodobacter sphaeroides lipid A (RSLA) and a blocking monoclonal antibody to CD14 (60bca). HPE increased monocyte secretion of IL-8, ENA-78, and MCP-1. Heat treatment of HPE did not reduce its ability to activate monocytes. Purified H. pylori LPS also stimulated monocyte chemokine production but was 1,000-fold less potent than Salmonella minnesota lipid A. RSLA blocked H. pylori LPS-induced monocyte IL-8 release in a dose-dependent fashion (maximal inhibition 82%, P < 0.001). RSLA also inhibited HPE-induced IL-8 release (by 93%, P < 0.001). The anti-CD14 monoclonal antibody 60bca substantially inhibited IL-8 release from HPE-stimulated monocytes (by 88%, P < 0.01), whereas the nonblocking anti-CD14 monoclonal antibody did not. These experiments with potent and specific LPS inhibitors indicate that the main monocyte-stimulating factor in HPE is LPS. H. pylori LPS, acting through CD14, stimulates human monocytes to release the neutrophil-activating chemokines IL-8 and ENA-78 and the monocyte-activating chemokine MCP-1. Despite its low relative potency, H. pylori LPS may play an important role in the pathogenesis of H. pylori gastritis.

UI MeSH Term Description Entries
D008050 Lipid A Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties.
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D011971 Receptors, Immunologic Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere. Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012242 Rhodobacter sphaeroides Spherical phototrophic bacteria found in mud and stagnant water exposed to light. Rhodopseudomonas sphaeroides,Rhodobacter spheroides,Rhodopseudomonas spheroides
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D016209 Interleukin-8 A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells. CXCL8 Chemokine,Chemokine CXCL8,Chemotactic Factor, Macrophage-Derived,Chemotactic Factor, Neutrophil, Monocyte-Derived,IL-8,Neutrophil-Activating Peptide, Lymphocyte-Derived,Neutrophil-Activating Peptide, Monocyte-Derived,AMCF-I,Alveolar Macrophage Chemotactic Factor-I,Anionic Neutrophil-Activating Peptide,Chemokines, CXCL8,Chemotactic Factor, Neutrophil,Granulocyte Chemotactic Peptide-Interleukin-8,IL8,Monocyte-Derived Neutrophil Chemotactic Factor,Neutrophil Activation Factor,Alveolar Macrophage Chemotactic Factor I,Anionic Neutrophil Activating Peptide,CXCL8 Chemokines,CXCL8, Chemokine,Chemokine, CXCL8,Chemotactic Factor, Macrophage Derived,Chemotactic Peptide-Interleukin-8, Granulocyte,Granulocyte Chemotactic Peptide Interleukin 8,Interleukin 8,Lymphocyte-Derived Neutrophil-Activating Peptide,Macrophage-Derived Chemotactic Factor,Monocyte-Derived Neutrophil-Activating Peptide,Neutrophil Activating Peptide, Lymphocyte Derived,Neutrophil Activating Peptide, Monocyte Derived,Neutrophil Chemotactic Factor,Neutrophil-Activating Peptide, Anionic,Peptide, Anionic Neutrophil-Activating
D016480 Helicobacter pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus CAMPYLOBACTER, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus HELICOBACTER. It has been officially transferred to Helicobacter gen. nov. (see Int J Syst Bacteriol 1989 Oct;39(4):297-405). Campylobacter pylori,Campylobacter pylori subsp. pylori,Campylobacter pyloridis,Helicobacter nemestrinae
D054365 Chemokine CXCL5 A CXC chemokine that is predominantly expressed in EPITHELIAL CELLS. It has specificity for the CXCR2 RECEPTORS and is involved in the recruitment and activation of NEUTROPHILS. CXCL5 Chemokine,Chemokine (C-X-C Motif) Ligand 5 Protein,ENA-78 Chemokine,Endothelial Neutrophil-Activating Peptide 78,Epithelial-Cell-Derived Neutrophil Attractant-78,CXCL5, Chemokine,Chemokine, CXCL5,ENA 78 Chemokine,Endothelial Neutrophil Activating Peptide 78,Epithelial Cell Derived Neutrophil Attractant 78,Neutrophil Attractant-78, Epithelial-Cell-Derived

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