PMID- 9784544 OWN - NLM STAT- MEDLINE DCOM- 19981123 LR - 20240206 IS - 0019-9567 (Print) IS - 1098-5522 (Electronic) IS - 0019-9567 (Linking) VI - 66 IP - 11 DP - 1998 Nov TI - 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. PG - 5357-63 AB - 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. FAU - Bliss, C M Jr AU - Bliss CM Jr AD - Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA. FAU - Golenbock, D T AU - Golenbock DT FAU - Keates, S AU - Keates S FAU - Linevsky, J K AU - Linevsky JK FAU - Kelly, C P AU - Kelly CP LA - eng GR - GM54060/GM/NIGMS NIH HHS/United States GR - R01 GM054060/GM/NIGMS NIH HHS/United States GR - DK02128/DK/NIDDK NIH HHS/United States GR - DK54920/DK/NIDDK NIH HHS/United States GR - R37 GM054060/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (CXCL5 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL5) RN - 0 (Chemokines, CXC) RN - 0 (Interleukin-8) RN - 0 (Lipid A) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, Immunologic) RN - 0 (endotoxin receptor) SB - IM MH - Chemokine CCL2/*metabolism MH - Chemokine CXCL5 MH - *Chemokines, CXC MH - Helicobacter pylori/*immunology MH - Humans MH - Interleukin-8/*analogs & derivatives/antagonists & inhibitors/biosynthesis/*metabolism MH - Lipid A/pharmacology MH - Lipopolysaccharide Receptors/*metabolism MH - Lipopolysaccharides/antagonists & inhibitors/*metabolism/*pharmacology MH - Monocytes/drug effects/*immunology/metabolism MH - Receptors, Immunologic/metabolism/physiology MH - Rhodobacter sphaeroides MH - Up-Regulation/drug effects/immunology PMC - PMC108670 EDAT- 1998/10/24 02:14 MHDA- 2001/03/28 10:01 PMCR- 1998/11/01 CRDT- 1998/10/24 02:14 PHST- 1998/10/24 02:14 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1998/10/24 02:14 [entrez] PHST- 1998/11/01 00:00 [pmc-release] AID - 0023 [pii] AID - 10.1128/IAI.66.11.5357-5363.1998 [doi] PST - ppublish SO - Infect Immun. 1998 Nov;66(11):5357-63. doi: 10.1128/IAI.66.11.5357-5363.1998.