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.
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.
De Yang
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, Frederick, MD, USA.
Chen
Q
Q
Schmidt
A P
AP
Anderson
G M
GM
Wang
J M
JM
Wooters
J
J
Oppenheim
J J
JJ
Chertov
O
O
D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology; D054804:Cathelicidins; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054804:Cathelicidins; C105101:FPR2 protein, human; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide; D002118:Calcium