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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Anti-Bacterial Agents / metabolism*
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Anti-Bacterial Agents / pharmacology
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Antimicrobial Cationic Peptides / metabolism*
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Antimicrobial Cationic Peptides / pharmacology
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Calcium / metabolism
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Carrier Proteins / metabolism*
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Carrier Proteins / pharmacology
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Cathelicidins
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Cell Line, Transformed
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Cells, Cultured
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Chemotaxis, Leukocyte / drug effects
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Chemotaxis, Leukocyte / physiology*
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Epithelial Cells / metabolism
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Humans
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / physiology
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Monocytes / cytology
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Monocytes / drug effects
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Monocytes / physiology*
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Neutrophils / drug effects
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Neutrophils / metabolism
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Neutrophils / physiology*
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Receptors, Formyl Peptide
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Receptors, Lipoxin*
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Receptors, Peptide / genetics
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Receptors, Peptide / metabolism*
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects
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T-Lymphocytes / physiology*
Substances
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Anti-Bacterial Agents
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Antimicrobial Cationic Peptides
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Carrier Proteins
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Cathelicidins
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FPR2 protein, human
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Receptors, Formyl Peptide
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Receptors, Immunologic
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Receptors, Lipoxin
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Receptors, Peptide
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Calcium