Regulation of neutrophil superoxide production in sepsis
J. S. Solomkin, L. A. Cotta, J. K. Brodt and J. M. Hurst
Neutrophil superoxide production has been recognized as an important
pathway for microbicidal activity and regulation of the local inflammatory
environment. To investigate neutrophil superoxide production in sepsis, we
studied 22 patients with intra-abdominal infections, and correlated
superoxide production with chemotactic response and granular enzyme
content. Our results showed that neutrophils from infected patients had
specific loss of chemotactic response to C5a, and were deficient in the
granular enzymes, lysozyme, and beta-glucuronidase. Superoxide production
in response to opsonized zymosan was intact, but response to the
chemoattractant N-formyl-methionyl-leucyl-phenylalanine was markedly
depressed. This could be reversed in vitro by the addition of cytochalasin
B. These results suggest that down regulation of exocytosis of superoxide
to nonphagocytic stimuli occurs during sepsis, possibly protecting the host
from tissue injury due to oxide radical release. Superoxide response to
phagocytic stimulation was intact.
