Neutrophil response to endotoxin in the adult respiratory distress syndrome: role of CD14

American Journal of Respiratory Cell and Molecular Biology
P E ParsonsG S Worthen

Abstract

The role of both endotoxin and neutrophils in the development of acute lung injury continues to be debated. We hypothesized that early in the course of the development of the adult respiratory distress syndrome (ARDS) circulating neutrophils could be primed by endotoxin and that subsequent stimulated responses could be enhanced. Accordingly, neutrophils were isolated from patients at risk for and with ARDS. Unstimulated neutrophils from these patients neither produced nor were primed for superoxide production. Whereas phorbol myristate acetate-stimulated superoxide production was preserved, indicating that the cells were capable of a response, patient neutrophils produced less superoxide than did cells from normal subjects when primed with endotoxin (lipopolysaccharide [LPS]) and stimulated with formyl-methionyl-leucine-phenylalanine (FMLP), suggesting that there was a defect in the signal transduction mechanism for LPS. This was confirmed by the finding that patient neutrophils also had both decreased baseline CD14 expression and less CD14 upregulation after LPS stimulation compared with neutrophils from normal subjects. The mechanisms that could account for the decreased CD14 expression were studied in vitro. Neutrophils from...Continue Reading

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