Published ahead of print on November 17, 2005, doi:10.1165/rcmb.2005-0146OC Am. J. Respir. Cell Mol. Biol., Volume 34, Number 3, March 2006, 364-374 A more recent version of this article appeared on March 1, 2006
Submitted on April 18, 2005 Abnormalities in the Pulmonary Innate Immune System in Cystic FibrosisTheo J Moraes1*,1 Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Pediatric Respirology, The Hospital for Sick Children, Toronto, Ontario, Canada, 2 Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada, 3 Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, 4 Toronto Western Hospital Division Research Institute, University Health Network, Toronto, Ontario, Canada, 5 Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Toronto General Hospital, Toronto, Ontario, Canada * To whom correspondence should be addressed. E-mail: theo.moraes{at}utoronto.ca.
Pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but the basis for this susceptibility remains incompletely understood. One hypothesis is that CF airway surface liquid (ASL) is abnormal and interferes with neutrophil function. To study this possibility, we developed an in vitro system in which we collected ASL from primary cultures of normal and CF airway epithelial cells. Microbial killing was less efficient when bacteria were incubated with neutrophils in the presence of ASL from CF epithelia, as compared to normal ASL. Antimicrobial functions of human neutrophils were assessed in ASL from CF and normal epithelia using a combination of quantitative bacterial culture, flow cytometry, and microfluorescence imaging. The results of these assays of neutrophil function were indistinguishable in CF and normal ASL. In contrast, the direct bactericidal activity of ASL to Escherichia coli and to clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa was substantially less in CF than in normal ASL even when highly diluted in media of identical ionic strength. Taken together, these observations indicate that the antimicrobial properties of ASL in CF are compromised in a manner independent of ionic strength of the ASL and importantly, this effect is not mediated through a direct effect of the ASL on phagocyte function.
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
