Related Experiment Videos
Inhibition of neutrophil response by mepacrine
Abstract:
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.
Insights
Mepacrine inhibits neutrophil responses implicated in acute respiratory distress syndrome (ARDS) pulmonary complications. This drug may protect lung function by reducing neutrophil activation and dysfunction in ARDS.
Area of Science:
- Immunology
- Pharmacology
- Pulmonology
Background:
- Neutrophils play a key role in the lung damage seen in adult respiratory distress syndrome (ARDS).
- Mepacrine has shown potential in preclinical models to improve lung function in ARDS, possibly by modulating neutrophil activity.
Purpose of the Study:
- To investigate the specific effects of mepacrine on neutrophil functions relevant to ARDS.
- To compare mepacrine's inhibitory capacity across different neutrophil responses and stimuli.
Main Methods:
- Neutrophils were activated using phorbol myristate acetate (a soluble stimulus) and opsonized group B streptococcus (a particulate stimulus).
- Mepacrine's effect on superoxide production, chemotaxis (in response to n-formylmethionylleucylphenylalanine), and aggregation was measured.
- Inhibitory concentrations (IC50) were determined for each response.
Main Results:
- Mepacrine effectively inhibited neutrophil superoxide production against both soluble and particulate stimuli.
- Significant inhibition of neutrophil chemotaxis and aggregation was observed.
- The data indicated that mepacrine's inhibitory effect was dependent on the specific neutrophil response but not the stimulus type.
Conclusions:
- Mepacrine demonstrates broad inhibitory effects on key neutrophil functions involved in ARDS.
- These findings support the hypothesis that mepacrine confers protection against ARDS pulmonary complications through the inhibition of neutrophil activity.