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Neutrophils (PMN) represent a first line of defense in innate immunity via their ability to generate H₂O₂, which is the main oxygen-dependent bactericidal pathway to clear bacteria. There is abundant evidence that sepsis causes alteration of PMN function and excessive activation of complement. In rats developing sepsis after cecal ligation/puncture (CLP), blood PMN demonstrated a reduced binding capacity for C5a, loss of chemotactic activity, impaired phagocytosis and defective respiratory burst, the latter being due to the inability to assemble NADPH-oxidase and generate H₂O₂. Defective assembly of NADPH oxidase was found in PMN obtained from CLP rats, as defined by an inability to translocate p47^phox from the cytosol of PMN to the cell membrane. When PMN were exposed to C5a (for in vitro simulation of complement activation during sepsis), a progressive C5a - induced (time- and dose …