Role of pertussis toxin A subunit in neutrophil migration and vascular permeability.
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.
Brito
G A
GA
Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, Brazil.
Souza
M H
MH
Melo-Filho
A A
AA
Hewlett
E L
EL
Lima
A A
AA
Flores
C A
CA
Ribeiro
R A
RA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D037342:Pertussis Toxin; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D010566:Virulence Factors, Bordetella; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006632:Histamine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins