Proinflammatory activity of a cecropin-like antibacterial peptide from Helicobacter pylori.
Helicobacter pylori, the bacterial pathogen associated with gastritis and peptic ulcers, is highly successful in establishing infection in the human gastric mucosa, a process typically associated with massive infiltration of inflammatory cells. Colonization of the mucosa is suggested to be facilitated by H. pylori-produced cecropin-like peptides with antibacterial properties, giving the microbe a competitive advantage over other bacteria. We show that a cecropin-like antibacterial peptide from H. pylori, Hp(2-20), not only has a potent bactericidal effect but also induces proinflammatory activities in human neutrophils, e.g., upregulation of integrins (Mac-1), induction of chemotaxis, and activation of the oxygen radical producing NADPH-oxidase. Furthermore, we show that these effects are mediated through binding of Hp(2-20) to the promiscuous, G-protein-linked lipoxin A(4) receptor-formyl peptide-like receptor 1.
Bylund
J
J
The Phagocyte Research Laboratory, Department of Medical Microbiology and Immunology, University of Göteborg, Göteborg, Sweden. Johan.Bylund@microbio.gu.se
Christophe
T
T
Boulay
F
F
Nyström
T
T
Karlsson
A
A
Dahlgren
C
C
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000187:drug effects*; D019255:NADPH Oxidases / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C105101:FPR2 protein, human; C433783:Hp (2-20) protein, Helicobacter pylori; D016177:Macrophage-1 Antigen; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D019255:NADPH Oxidases