Identification of formyl peptides from Listeria monocytogenes and Staphylococcus aureus as potent chemoattractants for mouse neutrophils.
The prototypic formyl peptide N-formyl-Met-Leu-Phe (fMLF) is a major chemoattractant found in Escherichia coli culture supernatants and a potent agonist at human formyl peptide receptor (FPR) 1. Consistent with this, fMLF induces bactericidal functions in human neutrophils at nanomolar concentrations. However, it is a much less potent agonist for mouse FPR (mFPR) 1 and mouse neutrophils, requiring micromolar concentrations for cell activation. To determine whether other bacteria produce more potent agonists for mFPR1, we examined formyl peptides from Listeria monocytogenes and Staphylococcus aureus for their abilities to activate mouse neutrophils. A pentapeptide (N-formyl-Met-Ile-Val-Ile-Leu (fMIVIL)) from L. monocytogenes and a tetrapeptide (N-formyl-Met-Ile-Phe-Leu (fMIFL)) from S. aureus were found to induce mouse neutrophil chemotaxis at 1-10 nM and superoxide production at 10-100 nM, similar to the potency of fMLF on human neutrophils. Using transfected cell lines expressing mFPR1 and mFPR2, which are major forms of FPRs in mouse neutrophils, we found that mFPR1 is responsible for the high potency of fMIVIL and fMIFL. In comparison, activation of mFPR2 requires micromolar concentrations of the two peptides. Genetic deletion of mfpr1 resulted in abrogation of neutrophil superoxide production and degranulation in response to fMIVIL and fMIFL, further demonstrating that mFPR1 is the primary receptor for detection of these formyl peptides. In conclusion, the formyl peptides from L. monocytogenes and S. aureus are approximately 100-fold more potent than fMLF in activating mouse neutrophils. The ability of mFPR1 to detect bacterially derived formyl peptides indicates that this important host defense mechanism is conserved in mice.
Southgate
Erica L
EL
Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
He
Rong L
RL
Gao
Ji-Liang
JL
Murphy
Philip M
PM
Nanamori
Masakatsu
M
Ye
Richard D
RD
D000818:Animals; D002630:Chemotactic Factors / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D008089:Listeria monocytogenes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology*; D014162:Transfection
D002630:Chemotactic Factors; C469988:Fpr1 protein, mouse; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; C481578:formyl peptide receptor 2, mouse; D009240:N-Formylmethionine Leucyl-Phenylalanine