Promotion of Formyl Peptide Receptor 1-mediated Neutrophil Chemotactic Migration by Antimicrobial Peptides Isolated From the Centipede Scolopendra Subspinipes Mutilans

BMB Rep. 2016 Sep;49(9):520-5. doi: 10.5483/bmbrep.2016.49.9.098.

Abstract

We investigated the effects of two antimicrobial peptides (AMPs) isolated from Scolopendra subspinipes mutilans on neutrophil activity. Stimulation of mouse neutrophils with the two AMPs elicited chemotactic migration of the cells in a pertussis toxin-sensitive manner. The two AMPs also stimulated activation of ERK and Akt, which contribute to chemotactic migration of neutrophils. We found that AMP-stimulated neutrophil chemotaxis was blocked by a formyl peptide receptor (FPR) 1 antagonist (cyclosporin H); moreover the two AMPs stimulated the chemotactic migration of FPR1-expressing RBL-2H3 cells but not of vector-expressing RBL-2H3 cells. We also found that the two AMPs stimulate neutrophil migration in vivo, and that this effect is blocked in FPR1-deficient mice. Taken together, our results suggest that the two AMPs stimulate neutrophils, leading to chemotactic migration through FPR1, and the two AMPs will be useful for the study of FPR1 signaling and neutrophil activation. [BMB Reports 2016; 49(9): 520-525].

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Blotting, Western
  • Cell Line
  • Chemotaxis, Leukocyte / drug effects*
  • Cyclosporine / pharmacology
  • Diterpene Alkaloids
  • Drugs, Chinese Herbal / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Pertussis Toxin / toxicity
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Formyl Peptide / antagonists & inhibitors
  • Receptors, Formyl Peptide / genetics
  • Receptors, Formyl Peptide / metabolism*
  • Signal Transduction / drug effects

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Diterpene Alkaloids
  • Drugs, Chinese Herbal
  • Fpr1 protein, mouse
  • Receptors, Formyl Peptide
  • Cyclosporine
  • Pertussis Toxin
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • cyclosporin H
  • scolopendra alkaloids