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Role of pertussis toxin A subunit in neutrophil migration and vascular permeability
G A Brito1, M H Souza, A A Melo-Filho
1Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, Brazil.
Abstract:
The anti-inflammatory activity of pertussis toxin (Ptx) was compared to that of a noncatalytic mutant of pertussis toxin (9K/129G; Ptxm), which contains two amino acid substitutions in the A protomer, by using a rat model of inflammation. The toxins were administered intravenously 1 h prior to the injection of inflammatory stimuli. Ptx, but not Ptxm, inhibited neutrophil migration into peritoneal cavities in response to formyl-methionyl-leucyl-phenylalanine and lipopolysaccharide. The inhibitory effect of Ptx on neutrophil migration could not be explained by the ability of the toxin to induce leukopenia or neutropenia. The increase in skin vascular permeability induced by leukotriene B4, a powerful neutrophil chemotactic agent, was also inhibited only by Ptx. On the other hand, the increase in skin vascular permeability induced by histamine was potentiated by both toxins. These data show that Ptx inhibits neutrophil-mediated inflammation in vivo and that this effect is dependent on the ADP-ribosyltransferase activity of the A protomer.
Insights
Pertussis toxin (Ptx) effectively reduces neutrophil migration in inflammatory conditions. This anti-inflammatory effect is linked to Ptx's ADP-ribosyltransferase activity, unlike its inactive mutant.
Area of Science:
- Immunology
- Pharmacology
Background:
- Pertussis toxin (Ptx) is known to modulate immune responses.
- Understanding the specific mechanisms of Ptx's anti-inflammatory actions is crucial.
Purpose of the Study:
- To investigate the anti-inflammatory activity of Ptx compared to a noncatalytic mutant (Ptxm).
- To determine if Ptx inhibits neutrophil migration and vascular permeability in vivo.
Main Methods:
- A rat model of inflammation was utilized.
- Ptx and Ptxm were administered intravenously before inflammatory stimuli.
- Neutrophil migration and skin vascular permeability were assessed.
Main Results:
- Ptx, but not Ptxm, inhibited neutrophil migration induced by formyl-methionyl-leucyl-phenylalanine and lipopolysaccharide.
- Ptx inhibited leukotriene B4-induced vascular permeability, while both toxins potentiated histamine effects.
- The anti-inflammatory effect was independent of leukopenia or neutropenia.
Conclusions:
- Ptx exhibits significant anti-inflammatory activity in vivo by inhibiting neutrophil-mediated inflammation.
- This inhibitory effect is dependent on the ADP-ribosyltransferase activity of Ptx's A protomer.