title: Haemophilus influenzae induces neutrophil necrosis: a role in chronic obstructive pulmonary disease?
abstract: Noncapsulate Haemophilus influenzae is commonly found in the airways of patients with chronic obstructive pulmonary disease (COPD), both during stable disease and during exacerbations. Neutrophils are also found in large numbers in sputum from patients with COPD, which also contains released neutrophil products such as elastase. Why H. influenzae colonizes the lungs of patients with COPD in the presence of such large numbers of infiltrating neutrophils is not known. We set out to determine if abnormal interactions between H. influenzae and neutrophils could impact on COPD pathology. Noncapsulate H. influenzae clinical isolates were incubated in vitro with neutrophils from healthy volunteers, and respiratory burst activity, cytokine and chemokine production, phagocytosis and killing of bacteria, and neutrophil apoptosis and necrosis were measured. Neutrophil morphology was determined in sputum samples. H. influenzae were phagocytosed by neutrophils, thereby activating a respiratory burst and the secretion of the neutrophil chemoattractant IL-8. However, rather than kill the bacteria, the neutrophils themselves were killed (largely via necrosis) and released their granule contents into the extracellular environment. Neutrophil-derived IL-8, generated after the interaction of H. influenzae with neutrophils, may result in the further infiltration of neutrophils into the lungs, thereby amplifying the inflammatory response. However, the infiltrating neutrophils fail to kill the bacteria and instead release tissue-damaging products into the lung as they undergo necrosis. These results may help to explain the clinical picture in COPD.
authors.affiliation: School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Naylor
authors.forename: Denise
authors.initials: D
authors.lastname: Bakstad
authors.forename: Mark
authors.initials: M
authors.lastname: Biffen
authors.forename: Bob
authors.initials: B
authors.lastname: Thong
authors.forename: Peter
authors.initials: P
authors.lastname: Calverley
authors.forename: Stephen
authors.initials: S
authors.lastname: Scott
authors.forename: C Anthony
authors.initials: CA
authors.lastname: Hart
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Moots
authors.forename: Steven W
authors.initials: SW
authors.lastname: Edwards
mesh_terms: D006192:Haemophilus Infections / Q000378:metabolism; D006193:Haemophilus influenzae / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D009336:Necrosis; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000502:physiology; D013183:Sputum / Q000166:cytology
chemical_list: D016209:Interleukin-8; D017382:Reactive Oxygen Species; D019272:Leukocyte Elastase