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Protective effect of indomethacin against chemotactic deactivation of human neutrophils induced by formylated peptide
A Perianin1, M Gaudry, C Marquetty
1INSERM U. 294, Faculté de Médecine Xavier, Bichat, Paris, France.
Abstract:
The effects of the nonsteroidal antiinflammatory drug indomethacin on the parameters relating to the migration and respiratory burst of human polymorphonuclear leukocytes (PMN) were studied in an attempt to clarify the mechanism of this drug's action on PMN. At various concentrations below 200 micrograms/ml, indomethacin partially inhibited the spontaneous migration of PMN but did not alter the directional migration induced by C5a-activated serum. In the presence of N-formyl-methionyl-leucyl-phenylalanine (FMLP) as chemoattractant, directed PMN migration was either inhibited or stimulated by indomethacin, depending on FMLP concentration. When PMN migration was induced by the optimal and suboptimal FMLP concentrations of 10(-7) and 10(-8) M, indomethacin inhibited this migration, but when the high FMLP concentration of 10(-6) M depressed this migration by chemotactic deactivation, indomethacin restored it to its maximum. Both the inhibitory and stimulatory effects of indomethacin on FMLP-induced PMN migration were due to changes in the migration speed. Indomethacin also inhibited FMLP-induced changes in the shape of floating PMN, and in respiratory burst, as well as specific FMLP binding to PMN. In contrast, indomethacin did not alter the PMN respiratory burst induced by phorbol myristate acetate or C5a-activated serum. These data show that indomethacin is able to prevent the loss of PMN chemokinetic activity induced by formylated peptides and suggest that it might be useful for investigating the mechanism of peptide-induced chemotactic deactivation.
Insights
Indomethacin, an anti-inflammatory drug, affects human polymorphonuclear leukocyte (PMN) migration and respiratory burst. It can inhibit or stimulate PMN migration depending on chemoattractant concentration, offering insights into drug mechanisms.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Human polymorphonuclear leukocytes (PMN) are crucial immune cells involved in inflammation.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin are widely used, but their precise mechanisms on immune cell function require further elucidation.
- Understanding indomethacin's effects on PMN migration and respiratory burst is key to clarifying its anti-inflammatory actions.
Purpose of the Study:
- To investigate the impact of indomethacin on human PMN migration and respiratory burst.
- To elucidate the mechanism of indomethacin's action on PMN, particularly in response to chemoattractants.
- To explore indomethacin's role in modulating chemotactic deactivation.
Main Methods:
- Studied indomethacin's effects on spontaneous and directed PMN migration induced by C5a-activated serum and N-formyl-methionyl-leucyl-phenylalanine (FMLP).
- Assessed indomethacin's influence on PMN migration speed, shape changes, and respiratory burst.
- Examined specific FMLP binding to PMN in the presence of indomethacin.
Main Results:
- Indomethacin partially inhibited spontaneous PMN migration but did not affect C5a-induced migration.
- Indomethacin's effect on FMLP-induced migration varied, inhibiting at optimal/suboptimal concentrations and restoring migration at high FMLP concentrations that caused deactivation.
- Indomethacin altered migration speed, inhibited FMLP-induced shape changes and respiratory burst, and reduced FMLP binding, but did not affect PMA or C5a-induced respiratory bursts.
Conclusions:
- Indomethacin modulates PMN migration and respiratory burst, with concentration-dependent effects on FMLP-induced responses.
- Indomethacin prevents the loss of PMN chemokinetic activity induced by formylated peptides.
- The findings suggest indomethacin's potential utility in studying the mechanisms of peptide-induced chemotactic deactivation.