Pertussis toxin from Bordetella pertussis blocks neutrophil migration and neutrophil-dependent edema in response to inflammation.
Pertussis toxin (Ptx) is a hexameric protein with classical AB architecture produced by Bordetella pertussis. The aim of this study was to investigate the effect of Ptx on migration of polymorphonuclear leukocytes to site of inflammation and on cell-dependent edema. Ptx was purified from the supernatant of the culture medium of B. pertussis using hydroxylapatite chromatography and fetuin affinity chromatography. Ptx induced a maximal clustering of Chinese hamster ovary cells at concentrations as low as 0.1 ng/ml. Intravenous injection of Ptx (400 ng) significantly blocked the neutrophil migration induced by 200 ng of lipopolysaccharide (LPS from E. coli O111:B4; 2.27 +/- 0.13 vs 0.61 +/- 0.16 per 10(6) neutrophils/ml; P < 0.001; N = 5) and by 200 ng of formyl-methionyl-leucyl-phenylalanine (fMLP; 2.53 +/- 0.45 vs 0.75 +/- 0.14 per 10(6) neutrophils/ml; P < 0.01; N = 6) into the peritoneal cavities of male Wistar rats (weighing 150-180 g). In addition, Ptx (400 ng) pretreatment also blocked the edema induced by intraplantar injection of 100 micrograms carrageenin (delta increase in volume: 0.667 +/- 0.087 vs 0.313 +/- 0.058 ml; P < 0.01; N = 5) but not the edema induced by 100 micrograms dextran (delta increase in volume: 0.537 +/- 0.06 vs 0.385 +/- 0.076 ml; P > 0.05; N = 5). These data demonstrate that Ptx blocked neutrophil migration induced by a direct fMLP stimulus of a site of inflammation. In addition, this toxin blocks the indirect stimulus of LPS on neutrophil migration.(ABSTRACT TRUNCATED AT 250 WORDS)
Thomazzi
S M
SM
Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal do Ceara, Fortaleza, CE, Brasil.
Souza
M H
MH
Melo-Filho
A A
AA
Hewlett
E L
EL
Lima
A A
AA
Ribeiro
R A
RA
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D002351:Carrageenan / Q000494:pharmacology; D002464:Cell Migration Inhibition; D006224:Cricetinae; D003911:Dextrans / Q000494:pharmacology; D004487:Edema / Q000209:etiology; D007249:Inflammation / Q000150:complications / Q000503:physiopathology*; D008070:Lipopolysaccharides; D008297:Male; 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*
D000925:Anticoagulants; D003911:Dextrans; D008070:Lipopolysaccharides; D010566:Virulence Factors, Bordetella; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002351:Carrageenan; D037342:Pertussis Toxin