Signalling and cellular specificity of airway nitric oxide production in pertussis

Abstract

SummaryBordetella pertussis, the aetiological agent of whooping cough (pertussis), causes selective destruction of ciliated cells of the human airway mucosa. In a hamster tracheal organ culture model, B. pertussis causes identical cytopathology as does tracheal cytotoxin (TCT), a glycopeptide released by the bacterium. The damage caused by B. pertussis or TCT has been shown to be mediated via nitric oxide (NO?). Using immuno¯uorescence detection of the cytokine-inducible NO synthase (iNOS; NOS type II), we determined that B. pertussis induced epithelial NO? production exclusively within non-ciliated cells. This epithelial iNOS activation could be reproduced by the combination of TCT and endotoxin. However, neither TCT alone nor endotoxin alone was capable of inducing epithelial iNOS. This result mirrors the synergistic activity of TCT and endotoxin exhibited in monolayer cultures of tracheal epithelial cells. Therefore, TCT and endotoxin are both important virulence factors of B. pertussis, combining synergistically to cause the speci®c epithelial pathology of pertussis.

Epitope of the Vaccine-TypeBordetella pertussisStrain 186 Lipooligosaccharide and Antiendotoxin Activity of Antibodies Directed against the Terminal Pentasaccharide-Tetanus Toxoid Conjugate

“…Contrary evidence, presented by Flak and Goldman (8), indicated that B. pertussis endotoxin plays a crucial role in the selective destruction of the ciliated cells of human airway mucosa. In this process the endotoxin works synergistically with tracheal cytotoxin by inducing a toxic level of NO released from secretory epithelial cells.…”

“…It has been shown that LOS of B. pertussis is an antigen in natural infection (44), and new findings suggest that it is an important etiological factor in whooping cough pathogenesis and is directly involved in destruction of the ciliated cells of the human airways mucosa (8). LOS, working synergistically with tracheal cytotoxin, takes part in induction of nitric oxide synthase in nonciliated epithelial cells, and this is followed by NO release and subsequent damage to the ciliated cells (8,9).…”

Proinflammatory and Proapoptotic Activities Associated withBordetella pertussisFilamentous Hemagglutinin

“…The concept of synergy between multiple bacterial cell surface or secreted factors in exerting a proinflammatory effect is well established (5). This concept and the known activities of LPS guided our comparison of FHA with LPS in the assessment of these host cell responses.…”

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

“…NO F then diffuses to neighboring ciliated cells, which are much more susceptible to its damaging effects (250). TCT also functions synergistically with Bordetella LPS to induce the production of NO F within the airway epithelium (251). The ability to construct TCT-deficient mutants by expressing a heterologous ampG gene in Bordetella will allow this hypothesis to be tested by using in vivo models.…”