LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells

J Exp Med. 2000 Oct 2;192(7):1069-74. doi: 10.1084/jem.192.7.1069.

Abstract

We have previously shown that antimicrobial peptides like defensins have the capacity to mobilize leukocytes in host defense. LL-37 is the cleaved antimicrobial 37-residue, COOH-terminal peptide of hCAP18 (human cationic antimicrobial protein with a molecular size of 18 kD), the only identified member in humans of a family of proteins called cathelicidins. LL-37/hCAP18 is produced by neutrophils and various epithelial cells. Here we report that LL-37 is chemotactic for, and can induce Ca(2+) mobilization in, human monocytes and formyl peptide receptor-like 1 (FPRL1)-transfected human embryonic kidney 293 cells. LL-37-induced Ca(2+) mobilization in monocytes can also be cross-desensitized by an FPRL1-specific agonist. Furthermore, LL-37 is also chemotactic for human neutrophils and T lymphocytes that are known to express FPRL1. Our results suggest that, in addition to its microbicidal activity, LL-37 may contribute to innate and adaptive immunity by recruiting neutrophils, monocytes, and T cells to sites of microbial invasion by interacting with FPRL1.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Cationic Peptides / metabolism*
  • Antimicrobial Cationic Peptides / pharmacology
  • Calcium / metabolism
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology
  • Cathelicidins
  • Cell Line, Transformed
  • Cells, Cultured
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / physiology*
  • Epithelial Cells / metabolism
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / physiology
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / physiology*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Neutrophils / physiology*
  • Receptors, Formyl Peptide
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Lipoxin*
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology*

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Carrier Proteins
  • Cathelicidins
  • FPR2 protein, human
  • Receptors, Formyl Peptide
  • Receptors, Immunologic
  • Receptors, Lipoxin
  • Receptors, Peptide
  • Calcium