Published ahead of print on March 15, 2007, doi:10.1165/rcmb.2006-0375OC
© 2007 American Thoracic Society DOI: 10.1165/rcmb.2006-0375OC Haemophilus influenzae Induces Neutrophil NecrosisA Role in Chronic Obstructive Pulmonary Disease?School of Biological Sciences, and Division of Medical Microbiology and Genito-Urinary Medicine, School of Infection and Host Defence, University of Liverpool; Pulmonary and Rehabilitation Research Group, and Academic Rheumatology Unit, Clinical Science Centre, University Hospital Aintree, Liverpool; and AstraZeneca R&D Charnwood, Leicestershire, United Kingdom Correspondence and requests for reprints should be addressed to Prof S. W. Edwards, Biosciences Building, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK. E-mail: S.W.Edwards{at}liv.ac.uk 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.
Key Words: inflammation • apoptosis • IL-8
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