Abstract
The effects of granulocyte colony-stimulating factor (G-CSF) on the functional activities of circulating and lung-recruited neutrophils (PMNs) and alveolar macrophages (AMs) were studied in rats to further elucidate the mechanisms underlying G-CSF-enhanced pulmonary host defense. Animals received G-CSF or vehicle twice a day for 2 days, followed by an intratracheal challenge with endotoxin or saline. G-CSF up-regulated CD11b/c expression and mean channel fluorescence intensity of phagocytosis in circulating PMNs. G-CSF also enhanced phagocytic activities, reflected by both the percentage of phagocytosis and mean channel fluorescence intensity in lung-recruited PMNs and AMs in intratracheal endotoxin-challenged rats. The endotoxin-induced increase in pulmonary production of tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant was not affected by G-CSF pretreatment. These data demonstrate that G-CSF-enhanced pulmonary recruitment of PMNs is primarily based on the effects of G-CSF on the PMNs themselves, rather than the generation of certain chemotactic stimuli, i.e., cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha. The enhanced phagocytic activities of lung-recruited PMNs and AMs also augment pulmonary host defenses in G-CSF-pretreated animals.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bronchoalveolar Lavage Fluid / chemistry
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CD18 Antigens / immunology
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CD18 Antigens / metabolism
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Chemokines, CXC*
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Chemotactic Factors / immunology
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Chemotactic Factors / metabolism
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Endotoxins / immunology*
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Endotoxins / physiology
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Granulocyte Colony-Stimulating Factor / immunology*
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Granulocyte Colony-Stimulating Factor / physiology
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Growth Substances / immunology
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Growth Substances / metabolism
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Hydrogen Peroxide / immunology
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Hydrogen Peroxide / metabolism
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Immunity, Cellular / immunology*
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Immunity, Cellular / physiology
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Integrin alphaXbeta2 / immunology
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Integrin alphaXbeta2 / metabolism
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Intercellular Signaling Peptides and Proteins*
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Lung / cytology*
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Lung / immunology
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Lung / physiology
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Macrophage-1 Antigen / immunology
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Macrophage-1 Antigen / metabolism
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Macrophages, Alveolar / immunology
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Macrophages, Alveolar / physiology
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Male
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Neutrophils / immunology
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Neutrophils / physiology
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Phagocytosis / immunology
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Phagocytosis / physiology
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Rats
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Rats, Sprague-Dawley
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Time Factors
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
Substances
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CD18 Antigens
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Chemokines, CXC
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Chemotactic Factors
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Endotoxins
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Growth Substances
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Integrin alphaXbeta2
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Intercellular Signaling Peptides and Proteins
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Macrophage-1 Antigen
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Tumor Necrosis Factor-alpha
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Granulocyte Colony-Stimulating Factor
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Hydrogen Peroxide