Bacterial-induced release of inflammatory mediators by bronchial epithelial cells.
This review focuses on bacterial induction and release of inflammatory cytokines and adhesion molecules by human bronchial epithelial cells, with special reference to Haemophilus influenzae, a pathogen commonly associated with chronic bronchitis. Studies investigating the mechanisms underlying bacterial colonization of the airways and bacterial-induced chronic airway inflammation have suggested that these are likely to involve localization of bacteria to the site(s) of infection in the respiratory tract and induction of a local airway inflammation resulting in the initiation of epithelial damage. We have hypothesized that the gross airway epithelial damage observed in chronic infective lung disease is an indirect consequence of proteolytic enzymes and toxic oxygen radicals generated by large numbers of neutrophils infiltrating the airways. Furthermore, the infiltration and activation of the neutrophils is a consequence of increased release of proinflammatory mediators from the host respiratory epithelium, induced by bacterial products, such as endotoxin. This hypothesis is based on studies which have demonstrated that the concentrations of circulating cytokines, such as interleukin (IL)-8 and tumour necrosis factor-alpha (TNF-alpha), which have profound effects on neutrophil activity, are increased in endotoxaemia and that airway epithelial cells are a rich source of these cytokines. Support for this hypothesis is provided by studies of cultured human bronchial epithelial cells incubated either in the absence or presence of purified endotoxin preparations from nontypable and type b H. influenzae strains which have demonstrated that these endotoxins lead to significantly increased expression and/or release of proinflammatory mediators, including IL-6, IL-8, TNF-alpha and intercellular adhesion molecule-1 (ICAM-1). Treatment of the cells with steroids can downregulate the expression and/or release of these inflammatory mediators. Additionally, these studies have demonstrated that culture medium collected from endotoxin-treated cultures, 24 h after treatment, significantly increases neutrophil chemotaxis and adhesion to human endothelial cells in vitro.
Khair
O A
OA
Dept of Asthma and Allergic Respiratory Diseases, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London Chest Hospital, UK.
Davies
R J
RJ
Devalia
J L
JL
D001426:Bacterial Proteins / Q000502:physiology; D001980:Bronchi / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D001991:Bronchitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004727:Endothelium / Q000166:cytology; D004731:Endotoxins / Q000097:blood / Q000502:physiology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000382:microbiology; D006193:Haemophilus influenzae / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism; D010447:Peptide Hydrolases / Q000502:physiology; D017382:Reactive Oxygen Species / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004731:Endotoxins; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D010447:Peptide Hydrolases