Lipopolysaccharide-induced granule mobilization and priming of the neutrophil response to Helicobacter pylori peptide Hp(2-20), which activates formyl peptide receptor-like 1

• 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. Nystrom, 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.

Nyckelord

Amino Acid Sequence

Anti-Bacterial Agents/*immunology

Bacterial Proteins/*immunology

Cells

Cultured

Gelatinases/immunology

Helicobacter pylori/*immunology

Humans

Lipopolysaccharides/*immunology/pharmacology

Macrophage-1 Antigen/immunology

Molecular Sequence Data

Neutrophils/drug effects/*immunology

Organelles

Peptide Fragments/*immunology

Peptides/immunology

Receptors

Complement 3b/immunology

Receptors

Formyl Peptide

Receptors

Immunologic/*immunology

*Receptors

Lipoxin

Receptors

Peptide/*immunology

Subcellular Fractions

Superoxides

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)