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- Albrecht, Eva, et al.
(författare)
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Telomere length in circulating leukocytes is associated with lung function and disease
- 2014
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 43:4, s. 983-992
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Tidskriftsartikel (refereegranskat)abstract
- Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.
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| 2. |
- Hell, Eva
(författare)
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Studies on Staphylococcus epidermidis biofilm formation and the bacterial interaction with the human cathelicidin antimicrobial peptide LL-37
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The long-term use of central venous catheters for delivering nutrients and drugs in preterm neonates has been related to nosocomial infections. The majority of late-onset sepsis in very preterm infants (<28 gestational weeks) are caused by Gram positive bacteria. Coagulase- negative staphylococci (CoNS) are responsible for almost the half of these cases. Staphylococcus epidermidis is the most prevalent bacteria identified from CoNS bacteraemia and biofilm production is found to be the main determinant of persistent infection. The major host defense peptide LL-37 is the only cathelicidin antimicrobial peptide that exists in humans. The peptide is broadly distributed in the human body and possesses several additional functions related to host defense. As a cathionic peptide, it interacts with the negatively charged bacterial surface. LL-37 is shown to inhibit biofilm formation and regulates biofilm-associated gene expression in Pseudomonas aeruginosa in vitro. In Paper I, we showed that S. epidermidis strains obtained from bloodstream infection in preterm infants had different characteristics than the skin strains isolated from healthy term neonates. The blood isolates were equipped with an invasive genetic element IS256 and showed higher antimicrobial resistance compared with the skin isolates. However, vancomycin resistance was not detected among any of the strains. We also observed short and long filament- like structures on the cell surface of S. epidermidis. These filaments were involved in the attachment to the catheter surface and also in cell to cell attachment and/or communication. Our in vitro studies in Paper II and Paper III, revealed that physiological LL-37 peptide concentrations, below those that kill or inhibit growth of the free-floating bacteria, inhibited S. epidermidis attachment and biofilm formation on abiotic surfaces. In Paper III, we observed that the peptide regulates genes involved in the biofilm formation. In Paper IV, we found that the circulating serum level of hCAP18/LL-37 was similar in preterm and term neonates at birth and both the inactive protein and the active peptide were detectable independent of the gestational time. We observed positive correlation between maternal and infant peptide concentration. This may indicate that the peptide passes over early during pregnancy. In summary, our work revealed that S. epidermidis strains that cause bloodstream infection in preterm infants are more virulent compared with skin strains in term neonates. Physiological concentration of the human cathionic peptide LL-37 had inhibitory effect on S. epidermidis biofilm formation by regulating biofilm genes. The similar LL-37 peptide concentration in preterm and term infants’ blood might suggest that these neonate’s vulnerability is not connected to the lower antimicrobial peptide level at birth.
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