Various inflammatory diseases are characterized by tissue infiltration of neutrophils. Chemokines recruit and activate leukocytes, but neutrophils are traditionally known to be restricted in their ...chemokine receptor (CR) expression repertoire. Neutrophils undergo phenotypic and functional changes under inflammatory conditions, but the mechanisms regulating CR expression of infiltrated neutrophils at sites of chronic inflammation are poorly defined. Here we show that infiltrated neutrophils from patients with chronic inflammatory lung diseases and rheumatoid arthritis highly express CR on their surface that are absent or only marginally expressed on circulating neutrophils, i.e., CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4, as measured by flow cytometry, immunohistochemistry, and confocal microscopy. The induction of CR surface expression on infiltrated neutrophils was functionally relevant, because receptor activation by chemokine ligands ex vivo modulated neutrophil effector functions such as respiratory burst activity and bacterial killing. In vitro studies with isolated neutrophils demonstrated that the surface expression of CR was differentially induced in a cytokine-mediated, protein synthesis-dependent manner (CCR1, CCR3), through Toll-like (CXCR3) or NOD2 (CCR5) receptor engagement, through neutrophil apoptosis (CCR5, CXCR4), and/or via mobilization of intracellular CD63(+) granules (CXCR3). CR activation on infiltrated neutrophils may represent a key mechanism by which the local inflammatory microenvironment fine-tunes neutrophil effector functions in situ. Since the up-regulation of CR was exclusively found on infiltrated neutrophils at inflammatory sites in situ, the targeting of these G protein-coupled receptors may have the potential to site-specifically target neutrophilic inflammation.
Background Altered intakes of n-3 and n-6 polyunsaturated fatty acids were suggested to modulate allergic disease, but intervention trials yielded inconclusive results. Because allergies are primed ...in early infancy and in utero , the fetus might be more accessible to nutritional intervention strategies. Objective We sought to investigate how supplementation of pregnant women with a fish oil (FO) preparation modulates allergy-related immune parameters in mothers and offspring. Methods We performed a multicenter, randomized, double-blind, placebo-controlled trial. Three hundred eleven pregnant women received daily either FO with 0.5 g of docosahexaenoic acid and 0.15 g of eicosapentaenoic acid, 400 μg of methyl-tetra-hydrofolic acid, both, or placebo from the 22nd gestational week. TH 1/TH 2-related molecules were quantified in 197 maternal and 195 cord blood samples by using real-time RT-PCR. Data are given as geometric means 95% CIs. Results FO supplementation was associated with increased TGF-β mRNA in maternal (0.85 0.8-0.89; placebo: 0.68 0.64-0.72) and cord blood (0.85 0.81-0.9; placebo: 0.75 0.71-0.79). IL-1 (0.69 0.66-0.73; placebo: 0.83 0.79-0.88) and IFN-γ (0.54 0.51-0.57; placebo: 0.65 0.61-0.69) were decreased in mothers only ( P < .001). Cord blood mRNA levels of IL-4 (0.54 0.52-0.57; placebo: 0.64 0.61-0.68), IL-13 (0.61 0.58-0.65; placebo: 0.85 0.80-0.89), CCR4 (0.70 0.67-0.73; placebo: 0.88 0.84-0.92; all P < .001), and natural killer ( P < .001) and CCR3+ CD8+ T cells ( P < .04) were decreased in the FO group. Conclusion Supplementation with FO during pregnancy is associated with decreased mRNA levels of TH 2-related molecules in the fetus and decreased maternal inflammatory cytokines. We speculate that both effects are mediated by TGF-β.
•UHPLC-QqToF-MS method using pre-column derivatization for amino acid analysis.•Discussion of the advantages of the implemented MS detection over FLD.•Enantioseparation of D and L isomers with ...OPA/IBLC.•No detection of matrix interferences in biological samples.•Superb sensitivity for trace level analysis of D-amino acids.
The growing scientific attention in the biological function of D-amino acids leads to an increasing analytical interest for enantiomeric amino acid separation, which is still very challenging due to the lack of sufficiently sensitive, high-throughput analytical methods that can cope with often occurring matrix interferences and very low D-amino acid concentrations. Here, enantioseparation can benefit from improved resolution and chromatographic speed offered by modern UHPLC techniques and the precision of MS detection. We developed a RP-UHPLC-QqToF-MS method using pre-column OPA/IBLC derivatization for very precise discrimination of amino acids enantiomers. The method shows a superb sensitivity with limits of detection in the range of several pmol/l. It has neither shown matrix inferences in the tested very complex biological matrices (serum, plasma, urine and gut) nor stability or racemization problems.
Knowing the molecular makeup of an organ system is required for its in-depth understanding. We analyzed the molecular repertoire of the adult tracheal system of the fruit fly
using transcriptome ...studies to advance our knowledge of the adult insect tracheal system. Comparing this to the larval tracheal system revealed several major differences that likely influence organ function. During the transition from larval to adult tracheal system, a shift in the expression of genes responsible for the formation of cuticular structure occurs. This change in transcript composition manifests in the physical properties of cuticular structures of the adult trachea. Enhanced tonic activation of the immune system is observed in the adult trachea, which encompasses the increased expression of antimicrobial peptides. In addition, modulatory processes are conspicuous, in this case mainly by the increased expression of G protein-coupled receptors in the adult trachea. Finally, all components of a peripheral circadian clock are present in the adult tracheal system, which is not the case in the larval tracheal system. Comparative analysis of driver lines targeting the adult tracheal system revealed that even the canonical tracheal driver line
(
)
is not able to target all parts of the adult tracheal system. Here, we have uncovered a specific transcriptome pattern of the adult tracheal system and provide this dataset as a basis for further analyses of the adult insect tracheal system.
BACKGROUND: Pregnant women usually meet their increased energy needs but do not always meet their increased micronutrient requirements. The supply of both folic acid and docosahexaenoic acid (DHA) ...has been related to positive pregnancy and infant outcomes. OBJECTIVE: We aimed to assess whether fish-oil (FO) supplementation with or without folate from gestation week 22 to birth improves maternal and fetal n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) status. DESIGN: We conducted a multicenter (Germany, Hungary, and Spain), randomized, double-blind, 2 x 2 factorial, placebo-controlled trial. From gestation week 22 until delivery, 311 pregnant women received daily a preparation with FO 0.5 g DHA and 0.15 g eicosapentaenoic acid (EPA), 400 μg methyltetrahydrofolic acid (MTHF), FO with MTHF, or placebo. Outcome measures included maternal and cord plasma DHA and EPA contents at gestation weeks 20 and 30 and at delivery, indicators of pregnancy outcome, and fetal development. RESULTS: FO significantly (P < 0.001) increased maternal DHA and EPA (% by wt), as shown by 3-factor repeated-measures ANOVA (ie, MTHF, FO, and time) with adjustment for maternal baseline DHA and EPA. In addition, FO significantly (P < 0.001) increased cord blood DHA (% by wt; 2-factor ANOVA). MTHF was significantly (P = 0.046) associated with increased maternal DHA (% by wt). There was no FO x MTHF interaction for the time course of DHA or EPA (P = 0.927 and 0.893). Pregnancy outcomes and fetal development did not differ significantly among the intervention groups. CONCLUSIONS: FO supplementation from gestation week 22 until delivery improves fetal n-3 LC-PUFA status and attenuates depletion of maternal stores. MTHF may further enhance maternal n-3 LC-PUFA proportions.
The airway epithelial cells and overlying layer of mucus are the first point of contact for particles entering the lung. The severity of environmental contributions to pulmonary disease initiation, ...progression, and exacerbation is largely determined by engagement with the airway epithelium. Despite the cellular cross-talk and cargo exchange in the microenvironment, epithelial cells produce miRNAs associated with the regulation of airway features in asthma. In line with this, there is evidence indicating miRNA alterations related to their multifunctional regulation of asthma features in the conducting airways. In this review, we discuss the cellular components and functions of the airway epithelium in asthma, miRNAs derived from epithelial cells in disease pathogenesis, and the cellular exchange of miRNA-bearing cargo in the airways.
Increasing knowledge of the microbiome has led to significant advancements in the agrifood system. Case studies based on microbiome applications have been reported worldwide and, in this review, we ...have selected 14 success stories that showcase the importance of microbiome research in advancing the agrifood system. The selected case studies describe products, methodologies, applications, tools, and processes that created an economic and societal impact. Additionally, they cover a broad range of fields within the agrifood chain: the management of diseases and putative pathogens; the use of microorganism as soil fertilizers and plant strengtheners; the investigation of the microbial dynamics occurring during food fermentation; the presence of microorganisms and/or genes associated with hazards for animal and human health (e.g., mycotoxins, spoilage agents, or pathogens) in feeds, foods, and their processing environments; applications to improve HACCP systems; and the identification of novel probiotics and prebiotics to improve the animal gut microbiome or to prevent chronic non-communicable diseases in humans (e.g., obesity complications). The microbiomes of soil, plants, and animals are pivotal for ensuring human and environmental health and this review highlights the impact that microbiome applications have with this regard.
Patients with chronic obstructive pulmonary disease (COPD) and in particular smokers are more susceptible to respiratory infections contributing to acute exacerbations of disease. The ...immunoproteasome is a specialized type of proteasome destined to improve major histocompatibility complex (MHC) class I-mediated antigen presentation for the resolution of intracellular infections.
To characterize immunoproteasome function in COPD and its regulation by cigarette smoke.
Immunoproteasome expression and activity were determined in bronchoalveolar lavage (BAL) and lungs of human donors and patients with COPD or idiopathic pulmonary fibrosis (IPF), as well as in cigarette smoke-exposed mice. Smoke-mediated alterations of immunoproteasome activity and MHC I surface expression were analyzed in human blood-derived macrophages. Immunoproteasome-specific MHC I antigen presentation was evaluated in spleen and lung immune cells that had been smoke-exposed in vitro or in vivo.
Immunoproteasome and MHC I mRNA expression was reduced in BAL cells of patients with COPD and in isolated alveolar macrophages of patients with COPD or IPF. Exposure of immune cells to cigarette smoke extract in vitro reduced immunoproteasome activity and impaired immunoproteasome-specific MHC I antigen presentation. In vivo, acute cigarette smoke exposure dynamically regulated immunoproteasome function and MHC I antigen presentation in mouse BAL cells. End-stage COPD lungs showed markedly impaired immunoproteasome activities.
We here show that the activity of the immunoproteasome is impaired by cigarette smoke resulting in reduced MHC I antigen presentation. Regulation of immunoproteasome function by cigarette smoke may thus alter adaptive immune responses and add to prolonged infections and exacerbations in COPD and IPF.
Background It is currently discussed whether allergic sensitization may start in utero under the influence of the maternal immune system and environmental determinants. Objective To investigate the ...relationship between allergen-specific cord blood (CB) IgE levels, parental sensitization, CB cytokine production, and environmental influences. Methods As part of an ongoing multicenter birth cohort study, allergen-specific IgE antibodies against 20 common seasonal, perennial, and food allergens were measured in blood samples from 922 neonates, 922 mothers, and 835 fathers. Supernatants from stimulated CB cells were assessed for the production of IL-5, IFN-γ, IL-10, and TNF-α. Results Allergen-specific IgE antibodies were detectable in 23.9% of newborns. Contamination with maternal serum was excluded by several means of analyses, including the absence of IgA antibodies. Clear correlation between maternal and fetal IgE was found only for hen's egg, cow's milk, and soybean allergen. Fetal IgE correlated negatively with the level of IFN-γ production, but not with IL-5 and IL-10. Conclusion Allergen-specific IgE antibodies most probably of fetal origin are detectable in CB and correlate with a lowered CB IFN-γ production.
Airway remodeling is an umbrella term for structural changes in the conducting airways that occur in chronic inflammatory lung diseases such as asthma or chronic obstructive pulmonary disease (COPD). ...The pathobiology of remodeling involves multiple mesenchymal and lymphoid cell types and finally leads to a variety of hardly reversible changes such as hyperplasia of goblet cells, thickening of the reticular basement membrane, deposition of collagen, peribronchial fibrosis, angiogenesis and hyperplasia of bronchial smooth muscle cells. In order to develop solutions for prevention or innovative therapies, these complex processes must be understood in detail which requires their deconstruction into individual building blocks. In the present manuscript we therefore focus on the role of the airway epithelium and introduce
Drosophila melanogaster
as a model. The simple architecture of the flies’ airways as well as the lack of adaptive immunity allows to focus exclusively on the importance of the epithelium for the remodeling processes. We will review and discuss genetic and environmentally induced changes in epithelial structures and molecular responses and propose an integrated framework of research for the future.
PDF
