title: Lipopolysaccharide-induced granule mobilization and priming of the neutrophil response to Helicobacter pylori peptide Hp(2-20), which activates formyl peptide receptor-like 1.
abstract: The cecropin-like bactericidal peptide Hp(2-20) from Helicobacter pylori induces activation of the NADPH oxidase in human neutrophils via formyl peptide receptor-like 1 (FPRL1) (J. Bylund, T. Christophe, F. Boulay, T. Nyström, A. Karlsson, and C. Dahlgren, Antimicrob. Agents Chemother. 45:1700-1704, 2001). Here we investigated the ability of bacterial lipopolysaccharide (LPS) to prime this response. Neutrophils treated with LPS for 30 min at 37 degrees C produced substantially more superoxide anion than control cells upon stimulation with Hp(2-20). Hence, LPS primed the cells for subsequent stimulation through FPRL1. To study the molecular background of this priming phenomenon, we measured the degrees of granule mobilization and concomitant receptor upregulation to the cell surface in LPS-treated cells. Exposure of complement receptors 1 and 3 as well as the formyl peptide receptor (FPR) was markedly increased after LPS treatment. Since approximately 60% of the gelatinase granules were mobilized while the specific granules were retained, we hypothesized that the gelatinase granules were potential stores of FPRL1. The presence of FPRL1 mainly in the gelatinase granules was confirmed by Western blotting of subcellular fractions of resting neutrophils. These results suggest that the mechanism behind the LPS-induced priming of FPRL1-mediated responses lies at the level of granule (receptor) mobilization.
authors: Phagocyte Research Laboratory, Department of Rheumatology, University of Göteborg, Göteborg, Sweden.
authors: Johan
authors: J
authors: Bylund
authors: Anna
authors: A
authors: Karlsson
authors: Francois
authors: F
authors: Boulay
authors: Claes
authors: C
authors: Dahlgren
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002478:Cells, Cultured; D018093:Gelatinases / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000276:immunology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D015388:Organelles; D010446:Peptide Fragments / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D017463:Receptors, Complement 3b / Q000276:immunology; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000276:immunology*; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000276:immunology*; D013347:Subcellular Fractions; D013481:Superoxides
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C105101:FPR2 protein, human; C433783:Hp (2-20) protein, Helicobacter pylori; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D010446:Peptide Fragments; D010455:Peptides; D017463:Receptors, Complement 3b; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide; D013481:Superoxides; D018093:Gelatinases