| 1. |
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| 2. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Padra, Médea, 1986, et al.
(författare)
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Increased MUC1 plus a larger quantity and complex size for MUC5AC in the peripheral airway lumen of long-term tobacco smokers
- 2020
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Ingår i: Clinical Science. - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 134:10, s. 1107-1125
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Tidskriftsartikel (refereegranskat)abstract
- There is little information on mucins versus potential regulatory factors in the peripheral airway lumen of long-term smokers with (LTS+) and without (LTS-) chronic obstructive pulmonary disease (COPD). We explored these matters in bronchoalveolar lavage (BAL) samples from two study materials, both including LTS+ and LTS- with a very similar historic exposure to tobacco smoke, and healthy non-smokers (HNSs; n=4-20/group). Utilizing slot blot and immunodetection of processed (filtered and centrifuged), as well as unprocessed BAL samples from one of the materials, we compared the quantity and fraction of large complexes of mucins. All LTS displayed an enhanced (median) level of MUC5AC compared with HNS. LTS- displayed a higher level of large MUC5AC complexes than HNS while LTS+ displayed a similar trend. In all LTS, total MUC5AC correlated with blood leukocytes, BAL neutrophil elastase and net gelatinase activity. Large mucin complexes accounted for most MUC5B, without clear group differences. In all LTS, total MUC5B correlated with total MUC5AC and local bacteria. In the same groups, large MUC5B complexes correlated with serum cotinine. MUC1 was increased and correlated with BAL leukocytes in all LTS whereas MUC2 was very low and without clear group differences. Thus, the main part of MUC5AC and MUC5B is present as large complexes in the peripheral airway lumen and historic as well as current exposure to tobacco smoke emerge as potential regulatory factors, regardless of COPD per se. Bacteria, leukocytes and proteinases also constitute potential regulatory factors, of interest for future therapeutic strategies.
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| 4. |
- Padra, Médea, 1986, et al.
(författare)
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Mucin Binding to Moraxella catarrhalis During Airway Inflammation is Dependent on Sialic Acid.
- 2021
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Ingår i: American journal of respiratory cell and molecular biology. - 1535-4989. ; 65:6, s. 593-602
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is associated with colonization by bacterial pathogens and repeated airway infections, leading to exacerbations and impaired lung function. The highly glycosylated mucins in the mucus lining the airways are an important part of the host defense against pathogens. However, mucus accumulation can contribute to COPD pathology. Here, we examined whether inflammation is associated with glycosylation changes that affect interactions between airway mucins and pathogens. We isolated mucins from lower airway samples (LAS, n=4-9) from long-term smokers with and without COPD and from never-smokers. The most abundant terminal glycan moiety was N-acetylneuraminic acid (Neu5Ac) among smokers with and without COPD and N-acetyl-hexoseamine among never-smokers. Moraxella catarrhalis bound to MUC5 mucins from smokers with and without COPD. M. catarrhalis binding correlated with inflammatory parameters and Neu5Ac content. M. catarrhalis binding was abolished by enzymatic removal of Neu5Ac. Furthermore, M. catarrhalis bound to α2-6 sialyl-lactose suggesting that α2-6 sialic acid contributes to M. catarrhalis binding to mucins. Further, we detected more M. catarrhalis binding to mucins from patients with pneumonia than to those from control subjects (n=8-13) and this binding correlated with C-reactive protein and Neu5Ac levels. These results suggest a key role of inflammation induced Neu5Ac in adhesion of M. catarrhalis to airway mucins. Inflammation induced ability of MUC5 mucins to bind M. catarrhalis is likely a host defense mechanism in the healthy lung, although it cannot be excluded that impaired mucociliary clearance limits the effectiveness of this defense in COPD patients.
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| 5. |
- Andersson, Anders, et al.
(författare)
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IL-36 Cytokines Promote Inflammation in the Lungs of Long-term Smokers
- 2021
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Ingår i: American journal of respiratory cell and molecular biology. - 1535-4989. ; 64:2, s. 173-182
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease with high morbidity and mortality. The IL-36 family are proinflammatory cytokines that are known to shape innate immune responses, including those critical to bacterial pneumonia. To determine whether IL-36 cytokines promote a proinflammatory milieu in the lungs of long-term smokers with and without COPD. Levels of IL-36 cytokines were measured in plasma and bronchoalveolar lavage fluid from subjects in a pilot study (n=23) of long-term smokers with and without COPD in vivo, and from a variety of lung cells (from 3-5 donors) stimulated with bacteria or cigarette smoke components in vitro. Pulmonary macrophages were stimulated with IL-36 cytokines in vitro, and chemokine and cytokine production was assessed. IL-36α and -γ are produced to varying degrees in murine and human lung cells in response to bacterial stimuli and cigarette smoke components in vitro. Moreover, while IL-36γ production is upregulated early after cigarette smoke stimulation and wanes over time, IL-36α production requires a longer duration of exposure. IL-36α and -γ are enhanced systemically and locally in long-term smokers with and without COPD, and local IL-36α levels display a positive correlation with declining ventilatory lung function and increasing proinflammatory cytokine levels. In vitro, IL-36α and -γ induce proinflammatory chemokines and cytokines in a concentration-dependent fashion that requires IL-36R and MyD88. IL-36 cytokine production is altered in long-term smokers with and without COPD and contributes to shaping a proinflammatory milieu in the lungs.
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| 6. |
- Aspholm-Hurtig, Marina, et al.
(författare)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 7. |
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| 8. |
- de Klerk, Nele, et al.
(författare)
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Lactobacilli Reduce Helicobacter pylori Attachment to Host Gastric Epithelial Cells by Inhibiting Adhesion Gene Expression
- 2016
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 84:5, s. 1526-1535
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Tidskriftsartikel (refereegranskat)abstract
- The human gastrointestinal tract, including the harsh environment of the stomach, harbors a large variety of bacteria, of which Lactobacillus species are prominent members. The molecular mechanisms by which species of lactobacilli interfere with pathogen colonization are not fully characterized. In this study, we aimed to study the effect of lactobacillus strains upon the initial attachment of Helicobacter pylori to host cells. Here we report a novel mechanism by which lactobacilli inhibit adherence of the gastric pathogen H. pylori. In a screen with Lactobacillus isolates, we found that only a few could reduce adherence of H. pylori to gastric epithelial cells. Decreased attachment was not due to competition for space or to lactobacillus-mediated killing of the pathogen. Instead, we show that lactobacilli act on H. pylori directly by an effector molecule that is released into the medium. This effector molecule acts on H. pylori by inhibiting expression of the adhesin-encoding gene sabA. Finally, we verified that inhibitory lactobacilli reduced H. pylori colonization in an in vivo model. In conclusion, certain Lactobacillus strains affect pathogen adherence by inhibiting sabA expression and thereby reducing H. pylori binding capacity.
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| 9. |
- Pournaras, N., et al.
(författare)
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Glucose Homeostasis in Relation to Neutrophil Mobilization in Smokers with COPD
- 2022
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Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - 1178-2005. ; 17, s. 1179-1194
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are common comorbidities in chronic obstructive pulmonary disease (COPD), but the underlying pathogenic mechanisms are poorly understood. Given that these morbidities all display increased neutrophil mobilization, the current study aimed to address whether glucose homeostasis relates to signs of neutrophil mobilization in COPD. Methods: The study population included healthy non-smokers (HNS) and long-term smokers without (LTS) and with COPD (LTS +COPD). No subject had T2DM or MetS. Serum cotinine was quantified to evaluate current smoking. Capillary blood glucose was measured after overnight fasting and during an oral glucose tolerance test (OGTT). Neutrophils were quantified in blood and bronchoalveolar lavage samples (BAL). The neutrophil-related cytokines IL-36 alpha, -beta and -gamma were quantified (ELISA) along with IL-6, IL-8, INF-gamma and CXCL10 (U-Plex (R)) in plasma and cell-free BAL fluid (BALF). In addition, we quantified neutrophil elastase (ELISA) and net proteinase activity (substrate assay) in BALF. Results: The LTS+COPD group had lower fasting glucose, greater change in glucose during OGTT and higher neutrophil concentrations in BAL and blood compared with HNS. Fasting glucose correlated in a positive manner with blood neutrophil concentration, forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) and FEV1 (% of predicted) in LTS+COPD. In this group, the concentration of IL-36 alpha in BALF correlated in a negative manner with fasting glucose, blood neutrophil concentration and FEV1, while the CXCL10 concentration in BALF correlated in a negative manner with glucose at the end of OGTT (120 min). We observed no corresponding correlations for neutrophil elastase, net proteinase or gelatinase activity. Conclusion: In smokers with COPD, altered glucose homeostasis is associated with local and systemic signs of increased neutrophil mobilization, but not with local proteinases. This suggests that other specific aspects of neutrophil mobilization constitute pathogenic factors that affect glucose homeostasis in COPD.
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| 10. |
- Stockfelt, Marit, et al.
(författare)
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Increased CD11b and Decreased CD62L in Blood and Airway Neutrophils from Long-Term Smokers with and without COPD
- 2020
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Ingår i: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 12:6, s. 480-489
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Tidskriftsartikel (refereegranskat)abstract
- There is incomplete mechanistic understanding of the mobilization of neutrophils in the systemic and local compartment in smokers with chronic obstructive pulmonary disease (COPD). In this pilot study, we characterized how the adhesion molecules CD11b and CD62L, surface markers indicative of priming, are altered as neutrophils extravasate, and whether surface density of CD11b and CD62L differs between long-term tobacco smokers (LTS) with and without COPD compared with healthy never-smokers (HNS). Unstimulated blood neutrophils from LTS with (<i>n</i> = 5) and without (<i>n</i> = 9) COPD displayed lower surface density of CD62L compared with HNS (<i>n</i> = 8). In addition, surface density of CD11b was higher in bronchoalveolar lavage (BAL) neutrophils from LTS without COPD compared with those with COPD and HNS. Moreover, in BAL neutrophils from all study groups, CD62L was lower compared with matched blood neutrophils. In addition, BAL neutrophils responded with a further decrease in CD62L to ex vivo TNF stimulation. Thus, neutrophils in the airway lumen display a higher state of priming than systemic neutrophils and bear the potential to be further primed by local cytokines even with no smoking or the presence of COPD, findings that may represent a universal host defense mechanism against local bacteria. Moreover, systemic neutrophils are primed in LTS regardless of COPD. Further studies in larger materials are warranted to determine whether the priming of neutrophils is protective against COPD or merely preceding it.
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