Inhibition of neutrophil response by mepacrine.
Clinical and experimental evidence supports neutrophil involvement in the pulmonary complications of adult respiratory distress syndrome. Preliminary evidence indicates that mepacrine salvages pulmonary function in experimental models of adult respiratory distress syndrome, possibly by inhibiting neutrophil activation [E. M. Canham et al., Am. Rev. resp. Dis. 127, 594 (1983)]. This study examines the effect of mepacrine on neutrophil responses involved in pulmonary dysfunction associated with adult respiratory distress syndrome. A comparison is made between the ability of mepacrine to inhibit a specific neutrophil response utilizing different stimuli and the ability to inhibit different neutrophil responses to a single stimulus. Neutrophils were activated by a soluble stimulus, phorbol myristic acetate, and a particulate stimulus, heat-inactivated opsonized group B streptococcus. Mepacrine inhibited superoxide production in response to both phorbol myristic acetate (IC50 = 5.3 +/- 1.2 microM) or opsonized group B streptococcus (16.1 +/- 1.7 microM). Chemotaxis in response to n-formylmethionylleucylphenylalanine was also inhibited (41.1 +/- 2.2 microM). Finally, aggregation stimulated by either streptococcus or phorbol myristic acetate was inhibited by mepacrine (73.0 +/- 9.8 microM and 77.0 +/- 19.2 microM respectively). A comparison of the IC50 values demonstrates that the inhibitory effect of mepacrine is response dependent and stimulus independent. The results of this study are consistent with the proposal that mepacrine protects against the pulmonary complications associated with adult respiratory distress syndrome by its action as an inhibitor of neutrophil function.
D002449:Cell Aggregation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011796:Quinacrine / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D013481:Superoxides; D011796:Quinacrine; D013755:Tetradecanoylphorbol Acetate