Logo Logo
Hilfe
Hilfe
Switch Language to English

Dwyer, Markryan; Shan, Qiang; D'Ortona, Samantha; Maurer, Rie; Mitchell, Robert; Olesen, Hanne; Thiel, Steffen; Hübner, Johannes und Gadjeva, Mihaela (2014): Cystic fibrosis sputum DNA has NETosis characteristics and neutrophil extracellular trap release is regulated by macrophage migration-inhibitory factor. In: Journal of Innate Immunity, Bd. 6, Nr. 6: S. 765-779 [PDF, 439kB]

[thumbnail of Cystic_Fibrosis_Sputum_DNA_Has_NETosis.pdf]
Vorschau
Download (439kB)

Abstract

Neutrophils are the main proinflammatory cell type in chronically infected lungs of cystic fibrosis (CF) patients; however, they fail to effectively clear the colonizing pathogens. Here, we investigated the molecular composition of non-mucoid and mucoid Pseudomonas aeruginosa-induced neutrophil extracellular traps (NETs) in vitro and compared them to the DNA-protein complexes present in the CF sputum. The protein composition of P. aeruginosa-induced NET fragments revealed that irrespective of the inducing stimuli, NET fragments were decorated with a conserved set of proteins. The DNA-protein complexes derived from CF sputum were consistent with NETosis and shared a similar protein signature, suggesting that the majority of the extracellular DNA was NET derived. The ability of polymorphonuclear leukocytes to produce NETs in response to P. aeruginosa was driven by macrophage migration-inhibitory factor (MIF) by promoting mitogen-activated protein kinase. Analysis of 132 CF patient samples revealed that elevated MIF protein levels correlated with poorer lung function. We suggest that targeting MIF by small molecular inhibitors might reduce the presence of extracellular DNA and serve as an adjunct to the use of antimicrobial drugs that could ultimately reduce bacterial fitness in the lungs during the later stages of CF disease.

Dokument bearbeiten Dokument bearbeiten