Abstract
Neuropeptide Y (NPY) increases survival in experimental septic shock, which might be mediated by cardiovascular and/or immunological effects. To study the latter hypothesis, we monitored blood leukocyte subsets over 96 h after intravenous (i.v.) application of LPS in chronically i.v.-cannulated rats. LPS induced a dramatic leukopenia at 4 h after challenge, which was blunted in NPY-treated animals by stabilizing granulocyte and T-lymphocyte numbers. In addition, NPY treatment prevented tissue immigration of monocytes at early time points and consecutively mobilized activated monocytes from the third day after challenge. RT-PCR and in vitro adhesion studies provided evidence for a NPY Y2 receptor-mediated effect on monocytes. Thus, NPY treatment has profound receptor-specific effects on the migration and adhesion of leukocytes under endotoxemic conditions.
Copyright 2004 Elsevier B.V.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / immunology
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Cell Adhesion / drug effects
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Cell Adhesion / genetics
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Cells, Cultured
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Chemotaxis, Leukocyte / drug effects*
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Chemotaxis, Leukocyte / immunology
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Down-Regulation / drug effects
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Down-Regulation / immunology
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Endotoxemia / chemically induced
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Endotoxemia / drug therapy*
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Endotoxemia / physiopathology
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Flow Cytometry
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Free Radicals / metabolism
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Injections, Intravenous
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Leukopenia / chemically induced
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Leukopenia / physiopathology
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Lipopolysaccharides
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Male
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Monocytes / drug effects*
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Monocytes / pathology
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Monocytes / physiology
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Neuropeptide Y / metabolism
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Neuropeptide Y / pharmacology*
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred Lew
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Receptors, Neuropeptide Y / genetics
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Receptors, Neuropeptide Y / metabolism*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / pathology
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Tumor Necrosis Factor-alpha / drug effects
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Free Radicals
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Lipopolysaccharides
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Neuropeptide Y
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RNA, Messenger
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Receptors, Neuropeptide Y
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Tumor Necrosis Factor-alpha
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neuropeptide Y2 receptor