Abstract
Defensins, a family of cationic, structurally related, antimicrobial peptides, contribute to host defense by disrupting the cytoplasmic membrane of microbes. Here we show that human neutrophil defensins selectively induce the migration of human CD4+/CD45RA+ naive and CD8+, but not CD4+/CD45RO+ memory, T cells. Moreover, human neutrophil defensins are chemotactic for immature human dendritic cells derived from either CD34+ progenitors or peripheral blood monocytes. Upon maturation induced by treatment with tumor necrosis factor alpha (TNF-alpha), dendritic cells lose their responsiveness to human neutrophil defensins. The chemotactic effect of human neutrophil defensins on both T and dendritic cells is pertussis toxin-sensitive, suggesting that a G(ialpha) protein-coupled receptor is responsible. Human neutrophil defensins are also chemotactic for immature murine dendritic cells. These data suggest that, in addition to their antimicrobial role, human neutrophil defensins also contribute to adaptive immunity by mobilizing T cells and dendritic cells.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Animals
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CD4-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / drug effects
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Cell Differentiation / drug effects
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Chemotactic Factors / pharmacology*
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Chemotaxis / drug effects*
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Defensins
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Dendritic Cells / cytology
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Dendritic Cells / drug effects*
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Female
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Fetal Blood / cytology
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GTP-Binding Protein alpha Subunits, Gi-Go / physiology
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Humans
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Immunologic Memory
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Infant, Newborn
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Leukocyte Common Antigens / analysis
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Mice
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Mice, Inbred C57BL
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N-Formylmethionine Leucyl-Phenylalanine / pharmacology
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Neutrophils / metabolism*
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Pertussis Toxin
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Proteins / pharmacology*
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Recombinant Proteins / pharmacology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / drug effects*
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Tumor Necrosis Factor-alpha / pharmacology
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Virulence Factors, Bordetella / pharmacology
Substances
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Chemotactic Factors
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Defensins
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Proteins
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Virulence Factors, Bordetella
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N-Formylmethionine Leucyl-Phenylalanine
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Granulocyte-Macrophage Colony-Stimulating Factor
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Pertussis Toxin
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Leukocyte Common Antigens
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GTP-Binding Protein alpha Subunits, Gi-Go