Human cathelicidin LL-37 is a chemoattractant for eosinophils and neutrophils that acts via formyl-peptide receptors

Int Arch Allergy Immunol. 2006;140(2):103-12. doi: 10.1159/000092305. Epub 2006 Mar 24.

Abstract

Background: Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by the presence of eosinophils and neutrophils. However, the mechanisms that mediate the influx of these cells are incompletely understood. Neutrophil products, including neutrophil elastase and antimicrobial peptides such as neutrophil defensins and LL-37, have been demonstrated to display chemotactic activity towards cells from both innate and adaptive immunity. However, chemotactic activity of LL-37 towards eosinophils has not been reported. Therefore, the aim of the present study was to investigate the chemotactic activity of LL-37 for eosinophils and to explore the mechanisms involved in LL-37-mediated attraction of neutrophils and eosinophils.

Methods: Neutrophils and eosinophils were obtained from venous blood of healthy donors. Chemotaxis was studied using a modified Boyden chamber technique. Involvement of formyl-peptide receptors (FPRs) was studied using the antagonistic peptide tBoc-MLP. Activation of the mitogen-activated protein kinase (MAPK) ERK1/2 was studied by Western blotting using antibodies directed against phosphorylated ERK1/2.

Results: Our results show that LL-37 chemoattracts both eosinophils and neutrophils. The FPR antagonistic peptide tBoc-MLP inhibited LL-37-induced chemotaxis. Whereas the FPR agonist fMLP activated ERK1/2 in neutrophils, LL-37 did not, indicating that fMLP and LL-37 deliver different signals through FPRs.

Conclusions: LL-37 displays chemotactic activity for eosinophils and neutrophils, and this activity is mediated via an FPR. These results suggest that LL-37 may play a role in inflammatory lung diseases such as asthma and COPD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Amino Acid Sequence
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antimicrobial Cationic Peptides / antagonists & inhibitors
  • Antimicrobial Cationic Peptides / pharmacology*
  • Chemotaxis, Leukocyte / drug effects*
  • Chemotaxis, Leukocyte / immunology
  • Enzyme Activation
  • Eosinophils / cytology
  • Eosinophils / drug effects*
  • Eosinophils / immunology
  • Ethanolamines / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Formoterol Fumarate
  • Humans
  • Molecular Sequence Data
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / cytology
  • Neutrophils / drug effects*
  • Neutrophils / enzymology
  • Neutrophils / immunology
  • Pertussis Toxin / pharmacology
  • Receptors, Formyl Peptide / immunology*

Substances

  • Adrenergic beta-Agonists
  • Antibodies, Monoclonal
  • Antimicrobial Cationic Peptides
  • Ethanolamines
  • Receptors, Formyl Peptide
  • ropocamptide
  • N-Formylmethionine Leucyl-Phenylalanine
  • Pertussis Toxin
  • Extracellular Signal-Regulated MAP Kinases
  • Mapk15 protein, rat
  • Formoterol Fumarate