title: Effect of tracheal cytotoxin from Bordetella pertussis on human neutrophil function in vitro.
abstract: The infiltration of neutrophils which phagocytose and kill microorganisms is an important defense mechanism against infections of the airways. Bordetella pertussis is a human respiratory pathogen which colonizes ciliated epithelium, causing whooping cough. We have investigated the effects of the peptidoglycan fragment tracheal cytotoxin (TCT) of B. pertussis on human neutrophil function in vitro. TCT (10(-6) to 10(-8) M) was toxic for human neutrophils, as measured by lactate dehydrogenase release and levels of intracellular ATP. TCT (10(-9) to 10(-15) M) did not stimulate neutrophil migration or chemiluminescence and did not affect neutrophil phagocytosis. Incubation of neutrophils for 20 min with TCT (10(-9) to 10(-11) M) significantly inhibited (P < 0.05) their subsequent migration toward the chemotactic factor N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 10(-9) M). Incubation of neutrophils for 20 min with TCT (10(-9) to 10(-15) M) significantly inhibited (P < 0.05) chemiluminescence stimulated by FMLP (10(-5) M). TCT (10(-6) to 10(-12) M) did not stimulate interleukin-1 alpha production by neutrophils or serum complement activation by the alternate pathway. We conclude that TCT at concentrations of < 10(-8) M affects important neutrophil functions and at higher concentrations is toxic. TCT may therefore contribute to the survival of B. pertussis within the airways in vivo.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
authors.forename: D R
authors.initials: DR
authors.lastname: Cundell
authors.forename: K
authors.initials: K
authors.lastname: Kanthakumar
authors.forename: G W
authors.initials: GW
authors.lastname: Taylor
authors.forename: W E
authors.initials: WE
authors.lastname: Goldman
authors.forename: T
authors.initials: T
authors.lastname: Flak
authors.forename: P J
authors.initials: PJ
authors.lastname: Cole
authors.forename: R
authors.initials: R
authors.lastname: Wilson
mesh_terms: D001886:Bordetella pertussis / Q000472:pathogenicity / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003167:Complement Activation; D003603:Cytotoxins / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D010457:Peptidoglycan / Q000633:toxicity*; D010587:Phagocytosis / Q000187:drug effects; D014132:Trachea / Q000382:microbiology; D010566:Virulence Factors, Bordetella / Q000633:toxicity*
chemical_list: D003603:Cytotoxins; D007375:Interleukin-1; D010457:Peptidoglycan; D010566:Virulence Factors, Bordetella; C059708:tracheal cytotoxin, Bordetella pertussis; D009240:N-Formylmethionine Leucyl-Phenylalanine