Degranulation inhibition. A potential mechanism for control of neutrophil superoxide production in sepsis
J. S. Solomkin, J. K. Brodt and F. P. Zemlan
Previous studies with neutrophils from patients with intra-abdominal sepsis
have provided convincing evidence of in vivo exposure to C5a. However, in
contradistinction to normal cells pretreated with C5a, patient cells showed
depressed superoxide response to N-formyl-methionyl-leucyl-phenyl-alanine
(FMLP) and enhanced FMLP receptor affinity. To identify possible mechanisms
responsible for these findings, we examined the effects of lysosomal
alkalinization with the weak base clindamycin on normal neutrophils with
and without C5a. Our results showed a specific suppression of FMLP-induced
superoxide production and a loss of low-affinity FMLP receptors. These
results occurred in the presence of clindamycin levels that did not
interfere with other cellular processes. These findings suggest that
regulation of neutrophil function during the course of intra-abdominal
sepsis may be due to effectors active both at the cell surface (C5a) and
within the lysosome. The clinical significance of our findings relates to a
possible mechanism for specific pharmacologic suppression of oxide-radical
production by neutrophils. Such oxide radicals are believed to be important
in the capillary injury accompanying severe sepsis.
