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