NADPH-oxidase activation in murine neutrophils via formyl peptide receptors.
Neutrophils play a key role at inflammatory sites where, in addition to destroying infecting microorganisms, they may also have deleterious effects on host tissues. Both activities involve activation of the NADPH-oxidase that produces bactericidal and tissue-destructive reactive oxygen species (ROS). We activated the murine NADPH-oxidase using different types of neutrophil activators and characterized the oxidative responses with respect to magnitude, localization, and kinetics. We show that agonist-induced activation of murine neutrophils results exclusively in extracellular release of ROS and no intracellular production could be detected. We also show that the formylated peptide, formyl-Met-Leu-Phe (fMLF), is a much less potent activator of the murine NADPH-oxidase than of the human analogue. Nevertheless, fMLF responses can be primed by pretreating the murine neutrophils with either cytochalasin B or bacterial lipopolysaccharide. Finally, we show that a synthetic hexapeptide, WKYMVM, is a more potent stimulus than fMLF for murine neutrophils and that these two agonists probably act via nonidentical high-affinity receptors.
Bylund
Johan
J
Department of Rheumatology and Inflammation Research, Göteborg University, Sweden. johan.bylund@microbio.gu.se
Samuelsson
Marie
M
Collins
L Vincent
LV
Karlsson
Anna
A
D000818:Animals; D003571:Cytochalasin B / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism*; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000819:agonists / Q000502:physiology*; D018000:Receptors, Peptide / Q000819:agonists / Q000502:physiology*
D008070:Lipopolysaccharides; D009842:Oligopeptides; D017382:Reactive Oxygen Species; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C113617:Trp-Lys-Tyr-Met-Val-Met; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases