Lipopolysaccharide-binding protein and CD14 are increased in the bronchoalveolar lavage fluid of smokers

Abstract

Lipopolysaccharide-binding protein (LBP) and CD14 contribute to the recognition of pathogens by cells, which triggers the activation of defence responses. Smoking is a risk factor for the development of chronic obstructive pulmonary disease (COPD) and respiratory infections. The current authors theorised that levels of LBP and CD14 in the lungs of smokers would be higher than those in the lungs of never-smokers. These elevated levels could affect host responses upon infection.LBP, soluble CD14 (sCD14) and interleukin (IL)-8 were detected by ELISA. Nuclear factor (NF)-kB, p38 and the inhibitor IkBa were studied by immunoassays. Gene expression was assessed by RT-PCR.Bronchoalveolar lavage levels of LBP and CD14 were significantly higher in smokers and COPD patients than in never-smokers, whereas levels of both proteins were not significantly different between smokers and COPD patients. IL-6, IL-1b and cigarette smoke condensate induced the expression of LBP and CD14 by airway epithelial cells. LBP and sCD14 inhibited the nontypeable Haemophilus influenzae (NTHi)-dependent secretion of IL-8 and the activation of NF-kB and p38 mitogen-activated protein kinase signalling pathways but they increased the internalisation of NTHi by airway epithelial cells.Thus, in the inflamed airways of smokers both proteins could contribute to inhibit bacteriadependent cellular activation without compromising the internalisation of pathogens by airway cells.

Impact of cigarette smoke exposure on host–bacterial pathogen interactions

“…Cell exposure to cigarette smoke diminishes phospho-Akt levels, which may account for the observed phagocytic deficiency; the same observations were made using immortalised macrophages and macrophages from bronchoalveolar lavage (BAL) from both smokers and COPD patients, compared with macrophages from neversmokers [41]. The levels of LPS-binding protein (LBP) and CD14 are higher in BAL from smokers and COPD patients than from never-smokers [86]. Furthermore, cigarette smoke induces the expression of LBP and CD14 in airway epithelial cells.…”

“…Furthermore, cigarette smoke induces the expression of LBP and CD14 in airway epithelial cells. Both proteins inhibit NTHi-dependent secretion of IL-8, and both NF-kB and p38 mitogen-activated protein kinase (MAPK) signalling pathways, but they increase NTHi entry into epithelial cells [86]. Given that NTHi can reside inside a late endosome-like compartment [87], LBP and CD14 may indeed contribute to NTHi colonisation by favouring bacterial location inside a subcellular niche.…”

Relative Contributions of Lipooligosaccharide Inner and Outer Core Modifications to Nontypeable Haemophilus influenzae Pathogenesis

“…Intracellular bacteria were found to colocalize with a fluid marker of acidic subcellular compartments (Lysotracker) in all cases (data not shown), as shown before for the wild-type strain (41). We and others have shown previously that NTHi infection triggers the secretion of proinflammatory cytokines by epithelial cells (53). We sought to determine the impact of LOS structure on IL-8 secretion by A549 cells.…”

Nontypeable Haemophilus influenzae Clearance by Alveolar Macrophages Is Impaired by Exposure to Cigarette Smoke

“…NTHI strain 398 (formerly strain 157925) is a clinical isolate from a COPD patient (Hospital Son Dureta, Spain) (25); NTHI strain 375 is an otitis media isolate (5). NTHI strains were grown on chocolate agar plates (Biomeriux) or on plates containing brain heart infusion (BHI) agar supplemented with hemin (10 g/ml) and ␤-nicotinamide adenine.…”