EFFECT OF TRACHEAL CYTOTOXIN FROM BORDETELLA-PERTUSSIS ON HUMAN NEUTROPHIL FUNCTION IN-VITRO

The infiltration of neutrophils which phagocytose and kill microorgani sms is an important defense mechanism against infections of the airway s. Bordetella pertussis is a human respiratory pathogen which colonize s ciliated epithelium, causing whooping cough. We have investigated th e 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 dehydroge nase 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 m in with TCT (10(-9) to 10(-11) M) significantly inhibited (P < 0.05) t heir subsequent migration toward the chemotactic factor N-formyl-L-met hionyl-L-leucyl-L-phenylalanine (FMLP; 10(-9) M). Incubation of neutro phils for 20 min with TCT (10(-9) to 10(-15) hi) significantly inhibit ed (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 t herefore contribute to the survival of B. pertussis within the airways in vivo.