Identification of Formyl Peptides from Listeria monocytogenes and Staphylococcus aureus as Potent Chemoattractants for Mouse Neutrophils

Abstract

The prototypic formyl peptide fMet‐Leu‐Phe (fMLF) is an E. coli‐derived chemoattractant for neutrophils. fMLF is a potent agonist of human formyl peptide receptor 1 (FPR1) and induces bactericidal functions of human neutrophils at nanomolar concentrations. However, mouse neutrophil activation requires fMLF concentrations in the micromolar range. To determine whether the mouse FPR is a physiologically relevant receptor for the detection of invading bacteria, formyl peptides derived from S. aureus and L. monocytogenes were examined. It was found that a tetrapeptide (fMIFL) from S. aureus and a pentapeptide (fMIVIL) from L. monocytogenes are potent agonists for the activation of mouse neutrophils. Both fMIFL and fMIVIL induced chemotaxis at concentrations of 1–10 nM and superoxide production at concentrations of 10–100 nM. Additionally, fMIFL and fMIVIL induced greater calcium mobilization than fMLF in mouse neutrophils. Mouse FPR1‐transfected rat basophilic leukemia cells (RBL) also responded to these peptides with greater induction of calcium mobilization and phosphorylation of ERK1/2 compared to fMLF. In conclusion, the S. aureus and L. monocytogenes derived peptides are approximately 100‐fold more potent than fMLF for the mouse FPR1. Differential recognition of formyl peptides from different bacterial strains by mouse neutrophils may be important for the innate immunity to these microorganisms.

The G-protein-coupled formylpeptide receptor FPR confers a more invasive phenotype on human glioblastoma cells

“…Owing to its expression in cells of the immune system and its interaction with bacterial chemotactic peptides, FPR was thought to participate in host defence against microbial infection. In support of this notion, mice depleted of the FPR analogue mFPR1 were more susceptible to infection by Listeria monocytogenes (Gao et al, 1999) that produced high affinity mFPR1 agonist peptides (Southgate et al, 2008). Recently, a number of host-derived chemotactic agonists of FPR have been identified, including formylpeptides potentially released by mitochondria of ruptured cells (Rabiet et al, 2005), annexin I produced by activated epithelia (Xia et al, 2002) and a neutrophil granule protein, cathepsin G (Sun et al, 2004).…”

VSOP/Hv1 proton channels sustain calcium entry, neutrophil migration, and superoxide production by limiting cell depolarization and acidification

“…fMIVIL was synthesized at UNIGE Peptides Synthesis Platform. This pentapeptide from Listeria monocytogenes was used instead of N-formylMet-Leu-Phe (fMLF) because it is 100-fold more potent than fMLF in activating mouse neutrophils (Southgate et al, 2008). Other chemicals were purchased from Sigma-Aldrich unless indicated otherwise.…”

“…4, A and D). To see whether the blunted SOCE could alter Ca 2+ responses to physiological agonists, we exposed cells to the bacterial peptide N-formyl-Met-Ile-Val-Ile-Leu (fMIVIL), a potent agonist of the mouse formyl peptide receptors (Southgate et al, 2008). In the absence of preactivation with PMA, fMIVIL evoked biphasic Ca 2+ elevations, reflecting an initial component of Ca 2+ release followed by a delayed component of Ca 2+ influx, as in human neutrophils (Demaurex et al, 1992).…”

Characterization of Quin-C1 for its anti-inflammatory property in a mouse model of bleomycin-induced lung injury

“…In neutrophils, mFpr1 and mFpr2 are most abundant at the transcript level, whereas the mouse Lxa4r transcript (encoded by mFpr-rs1) is found at a lower level [20] . The same expression pattern was seen in lung tissue devoid of circulating neutrophils.…”

“…Our results show an abundant expression of both mFpr1 and mFpr2 transcripts in mouse lung tissue, and the latter is reported to be a receptor for LXA4 [38] . Moreover, Quin-C1 induces calcium mobilization in mouse neutrophils, which express mFpr1 and mFpr2 transcripts [20] . Interestingly, our data indicate that both mFpr1 and mFpr2 are able to mediate Quin-C1-induced calcium mobilization and, based on the EC 50 value, mFpr1 is more potent.…”