Complement-Induced Impairment of Innate Immunity During Sepsis
| Autor: | Vaishalee A. Padgaonkar, Peter A. Ward, Richard W. Erickson, John T. Curnutte, J. Vidya Sarma, Markus Huber-Lang, Kristina T. Lu, Ellen M. Younkin, Stephanie R. McGuire, Ren Feng Guo |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Neutrophils Immunology MAP Kinase Kinase 1 Complement C5a Punctures Protein Serine-Threonine Kinases Neutrophil Activation Sepsis Cell membrane Antigens CD In vivo medicine Animals Humans Immunology and Allergy Rats Long-Evans Phosphorylation Cecum Ligation Receptor Anaphylatoxin C5a Respiratory Burst Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinase 3 Innate immune system NADPH oxidase biology Kinase Immune Sera Immunization Passive NADPH Oxidases Hydrogen Peroxide Phosphoproteins medicine.disease Immunity Innate Rats Receptors Complement Cell biology Cytosol medicine.anatomical_structure Phagocyte Bactericidal Dysfunction biology.protein Tetradecanoylphorbol Acetate Mitogen-Activated Protein Kinases Signal Transduction |
| Zdroj: | The Journal of Immunology. 169:3223-3231 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | This study defines the molecular basis for defects in innate immunity involving neutrophils during cecal ligation/puncture (CLP)-induced sepsis in rats. Blood neutrophils from CLP rats demonstrated defective phagocytosis and defective assembly of NADPH oxidase, the latter being due to the inability of p47phox to translocate from the cytosol to the cell membrane of neutrophils after cell stimulation by phorbol ester (PMA). The appearance of these defects was prevented by in vivo blockade of C5a in CLP rats. In vitro exposure of neutrophils to C5a led to reduced surface expression of C5aR and defective assembly of NADPH oxidase, as defined by failure in phosphorylation of p47phox and its translocation to the cell membrane, together with failure in phosphorylation of p42/p44 mitogen-activated protein kinases. These data identify a molecular basis for defective innate immunity involving neutrophils during sepsis. |
| Databáze: | OpenAIRE |
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