Cystic fibrosis (CF) lung disease is characterized by infection with Pseudomonas aeruginosa and a sustained accumulation of neutrophils. In this study, we analyzed 1) the expression of MyD88-dependent TLRs on circulating and airway neutrophils in P. aeruginosa-infected CF patients, P. aeruginosa-infected non-CF bronchiectasis patients, and noninfected healthy control subjects and 2) studied the regulation of TLR expression and functionality on neutrophils in vitro. TLR2, TLR4, TLR5, and TLR9 expression was increased on airway neutrophils compared with circulating neutrophils in CF and bronchiectasis patients. On airway neutrophils, TLR5 was the only TLR that was significantly higher expressed in CF patients compared with bronchiectasis patients and healthy controls. Studies using confocal microscopy and flow cytometry revealed that TLR5 was stored intracellularly in neutrophils and was mobilized to the cell surface in a protein synthesis-independent manner through protein kinase C activation or after stimulation with TLR ligands and cytokines characteristic of the CF airway microenvironment. The most potent stimulator of TLR5 expression was the bacterial lipoprotein Pam3CSK4. Ab-blocking experiments revealed that the effect of Pam3CSK4 was mediated through cooperation of TLR1 and TLR2 signaling. TLR5 activation enhanced the phagocytic capacity and the respiratory burst activity of neutrophils, which was mediated, at least partially, via a stimulation of IL-8 production and CXCR1 signaling. This study demonstrates a novel mechanism of TLR regulation in neutrophils and suggests a critical role for TLR5 in neutrophil-P. aeruginosa interactions in CF lung disease.
The CO2 methanation performance of a Ni catalyst supported on a Lewis basic (Mg,Al)Ox mixed oxide derived from a (Ni,Mg,Al)‐hydrotalcite‐like (HTL) precursor was investigated. The HTL structure of the precursor, synthesized by pH‐controlled coprecipitation, was confirmed by using XRD. Reduction at 900 °C led to metallic Ni particles supported on a spinel‐type (Mg,Al)Ox matrix. Catalytic measurements between 210 and 400 °C revealed a reproducible CO2 conversion into CH4. Kinetic analysis of the data in the lower temperature range resulted in an apparent activation energy of (83±7) kJ mol−1 for this reaction. After a latency period of 10 h, the catalyst showed excellent long‐term stability for up to 50 h on stream under methanation conditions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.