Defining biomarkers to predict symptoms in subjects with and without allergy under natural pollen exposure.

BACKGROUND: Pollen exposure induces local and systemic allergic immune responses in sensitized individuals, but nonsensitized individuals also are exposed to pollen. The kinetics of symptom expression under natural pollen exposure have never been systematically studied, especially in subjects without allergy. OBJECTIVE: We monitored the humoral immune response under natural pollen exposure to potentially uncover nasal biomarkers for in-season symptom severity and identify protective factors. METHODS: We compared humoral immune response kinetics in a panel study of subjects with seasonal allergic rhinitis (SAR) and subjects without allergy and tested for cross-sectional and interseasonal differences in levels of serum and nasal, total, and Betula verrucosa 1-specific immunoglobulin isotypes; immunoglobulin free light chains; cytokines; and chemokines. Nonsupervised principal component analysis was performed for all nasal immune variables, and single immune variables were correlated with in-season symptom severity by Spearman test. RESULTS: Symptoms followed airborne pollen concentrations in subjects with SAR, with a time lag between 0 and 13 days depending on the pollen type. Of the 7 subjects with nonallergy, 4 also exhibited in-season symptoms whereas 3 did not. Cumulative symptoms in those without allergy were lower than in those with SAR but followed the pollen exposure with similar kinetics. Nasal eotaxin-2, CCL22/MDC, and monocyte chemoattactant protein-1 (MCP-1) levels were higher in subjects with SAR, whereas IL-8 levels were higher in subjects without allergy. Principal component analysis and Spearman correlations identified nasal levels of IL-8, IL-33, and Betula verrucosa 1-specific IgG4 (sIgG4) and Betula verrucosa 1-specific IgE (sIgE) antibodies as predictive for seasonal symptom severity. CONCLUSIONS: Nasal pollen-specific IgA and IgG isotypes are potentially protective within the humoral compartment. Nasal levels of IL-8, IL-33, sIgG4 and sIgE could be predictive biomarkers for pollen-specific symptom expression, irrespective of atopy.

Pollen-Associated Microbiome Correlates with Pollution Parameters and the Allergenicity of Pollen.

Pollen allergies have been rapidly increasing over the last decades. Many allergenic proteins and non-allergenic adjuvant compounds of pollen are involved in the plant defense against environmental or microbial stress. The first aim of this study was to analyze and compare the colonizing microbes on allergenic pollen. The second aim was to investigate detectable correlations between pollen microbiota and parameters of air pollution or pollen allergenicity. To reach these aims, bacterial and fungal DNA was isolated from pollen samples of timothy grass (Phleum pratense, n = 20) and birch trees (Betula pendula, n = 55). With this isolated DNA, a terminal restriction fragment length polymorphism analysis was performed. One result was that the microbial diversity on birch tree and timothy grass pollen samples (Shannon/Simpson diversity indices) was partly significantly correlated to allergenicity parameters (Bet v 1/Phl p 5, pollen-associated lipid mediators). Furthermore, the microbial diversity on birch pollen samples was correlated to on-site air pollution (nitrogen dioxide (NO2), ammonia (NH3), and ozone (O3)). What is more, a significant negative correlation was observed between the microbial diversity on birch pollen and the measured NO2 concentrations on the corresponding trees. Our results showed that the microbial composition of pollen was correlated to environmental exposure parameters alongside with a differential expression of allergen and pollen-associated lipid mediators. This might translate into altered allergenicity of pollen due to environmental and microbial stress.

The effects of short- and long-term air pollutants on plant phenology and leaf characteristics.

Pollution adversely affects vegetation; however, its impact on phenology and leaf morphology is not satisfactorily understood yet. We analyzed associations between pollutants and phenological data of birch, hazel and horse chestnut in Munich (2010) along with the suitability of leaf morphological parameters of birch for monitoring air pollution using two datasets: cumulated atmospheric concentrations of nitrogen dioxide and ozone derived from passive sampling (short-term exposure) and pollutant information derived from Land Use Regression models (long-term exposure). Partial correlations and stepwise regressions revealed that increased ozone (birch, horse chestnut), NO2, NOx and PM levels (hazel) were significantly related to delays in phenology. Correlations were especially high when rural sites were excluded suggesting a better estimation of long-term within-city pollution. In situ measurements of foliar characteristics of birch were not suitable for bio-monitoring pollution. Inconsistencies between long- and short-term exposure effects suggest some caution when interpreting short-term data collected within field studies.

Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells.

BACKGROUND: Pollen allergens are delivered to epithelial surfaces of the upper respiratory tract in conjunction with multiple endogenous adjuvants. We previously demonstrated pollen-mediated modulation of cytokine and chemokine production of dendritic cells, contributing to a Th2-dominated micromilieu. As T helper cell differentiation not only depends on dendritic cell-derived cytokines but also on cell-cell-contact mediated mechanisms, we studied the expression of notch ligands and myeloid differentiation primary response protein 88 (MyD88) in dendritic cells matured in the presence of aqueous birch pollen extracts and pollen-associated E1-phytoprostanes. METHODS: Human monocyte-derived dendritic cells were stimulated with aqueous birch pollen extracts in the absence or presence of lipopolysaccharide, and mRNA expression levels of notch ligands delta-1 and -4, jagged-1 and -2 and of myd88 were determined. Regulation of Delta-4 and MyD88 by aqueous pollen extracts was assessed on protein level. The contribution of notch signaling to T helper cell differentiation was analyzed in allogeneic T cell stimulation assays. RESULTS: In immature dendritic cells, stimulation with pollen extracts resulted in an induction of both delta and jagged notch ligands. The lipopolysaccharide-induced up-regulation of delta-1 and -4 and of myd88 was decreased by aqueous pollen extracts, whereas jagged expression was induced. Reduction of Delta-4 and MyD88 by aqueous pollen extracts was confirmed on protein level. The Th2-skewing activity was contained in a fraction of aqueous pollen extracts enriched for molecules <3 kDa and was distinct from the previously identified E1-phytoprostanes. Reduction of notch signaling in dendritic cells matured in the presence aqueous pollen extract leads to inhibition of IL-10 and to induction of IL-5 production in naïve T cells differentiated by these dendritic cells. CONCLUSIONS: Pollen derived, non-allergenic factors reduce the dendritic cell's expression of Th1 instructing Delta-like notch ligands and of MyD88, thereby promoting Th2 skewing of T helper cell responses.

High environmental ozone levels lead to enhanced allergenicity of birch pollen.

BACKGROUND: Evidence is compelling for a positive correlation between climate change, urbanisation and prevalence of allergic sensitisation and diseases. The reason for this association is not clear to date. Some data point to a pro-allergenic effect of anthropogenic factors on susceptible individuals. OBJECTIVES: To evaluate the impact of urbanisation and climate change on pollen allergenicity. METHODS: Catkins were sampled from birch trees from different sites across the greater area of Munich, pollen were isolated and an urbanisation index, NO2 and ozone exposure were determined. To estimate pollen allergenicity, allergen content and pollen-associated lipid mediators were measured in aqueous pollen extracts. Immune stimulatory and modulatory capacity of pollen was assessed by neutrophil migration assays and the potential of pollen to inhibit dendritic cell interleukin-12 response. In vivo allergenicity was assessed by skin prick tests. RESULTS: The study revealed ozone as a prominent environmental factor influencing the allergenicity of birch pollen. Enhanced allergenicity, as assessed in skin prick tests, was mirrored by enhanced allergen content. Beyond that, ozone induced changes in lipid composition and chemotactic and immune modulatory potential of the pollen. Higher ozone-exposed pollen was characterised by less immune modulatory but higher immune stimulatory potential. CONCLUSION: It is likely that future climate change along with increasing urbanisation will lead to rising ozone concentrations in the next decades. Our study indicates that ozone is a crucial factor leading to clinically relevant enhanced allergenicity of birch pollen. Thus, with increasing temperatures and increasing ozone levels, also symptoms of pollen allergic patients may increase further.

Results after wisdom tooth transplantation. A retrospective study.

Wisdom tooth transplants offer youth the possibility of biologically fixed tooth replacement in cases of premolar agenesis or premature loss of a molar. In the present study, 57 transplants of third molars were reviewed and evaluated retrospectively on preoperative findings (root growth stages, extraction sites, indication for transplantation), on postoperative clinical findings (local gingivitis, periodontal probing values, tooth mobility, percussion sound and percussion pain) and on radiological findings (tertiary build-up of dentin, osseous periradicular conditions, progress of root growth). Only the transplants which healed with a vital pulp and in a periodontally healthy state were considered successful. Upper and lower wisdom teeth having 50% to 75% root growth progression were transplanted. The postoperative follow-up observation period averaged 26.4 months. The success of a wisdom tooth transplantation was not influenced by the root growth stage (p = 1), the extraction location of wisdom teeth (p = 0.45), or the feasibility for a transplantation (p = 0.56). Three teeth showed pulpal necrosis with apical periodontitis and were counted as failures. The success rate was rather high with 54 out of 57 transplants (94.7%), therefore wisdom tooth transplantations, with careful selection of a suitable graft and its gentle removal, can be described as a good predictable treatment.

Nutrient status: a missing factor in phenological and pollen research?

Phenology ranks among the best ecosystem processes for fingerprinting climate change since temperature explains a high percentage of the interannual or spatial variation in phenological onset dates. However, roles of other environmental variables, such as foliar nutrient concentrations, are far from adequately understood. This observational study examined the effects of air temperature and 11 nutrients on spring phenology of Betula pendula Roth (birch) along an urban-rural gradient in Munich, Germany, during the years 2010/2011. Moreover, the influence of temperature, nutrients, and air pollutants (NO2 and O3) on the amounts of pollen and catkin biomass in 2010 was evaluated. In addition to the influence of higher temperatures advancing phenological onset dates, higher foliar concentrations of potassium, boron, zinc, and calcium were statistically significantly linked to earlier onset dates. Since flushing of leaves is a turgor-driven process and all the influential nutrients are involved in cell extension, membrane function, and stability, there might be a reasonable physiological interpretation of the observed association. The amounts of pollen were negatively correlated with temperature, atmospheric NO2, and foliar iron concentration, suggesting that these variables restrict pollen production. The results of this study suggested an influence of nutritional status on both phenology and pollen production. The interaction of urbanization and climate change should be considered in the assessment of the impact of global warming on ecosystems and human health.

Pollen metabolome analysis reveals adenosine as a major regulator of dendritic cell-primed T(H) cell responses.

BACKGROUND: Water-soluble components from pollen modulate dendritic cell (DC) functions, such as IL-12 secretion and 3'-5'-cyclic adenosine monophosphate (cAMP) signaling and migration, possibly contributing to the establishment of a T(H)2-dominated immune response against pollen. Because these effects could not solely be attributed to the previously identified pollen-associated lipid mediators, the pollen metabolome was analyzed for candidate immunomodulatory substances. OBJECTIVE: We sought to perform an analysis of the effect of pollen-associated adenosine on DC function and T(H) cell differentiation. METHODS: Fractions of aqueous pollen extracts (APEs) were generated by means of ultrafiltration and were subjected simultaneously to biological tests and metabolome analysis (ultra-high-resolution mass spectrometry) and ultraperformance liquid chromatography. Effects of pollen-derived adenosine on monocyte-derived DC cAMP signaling, cytokine response, and capacity to differentiate T(H) cells were studied. RESULTS: The less than 3-kd fraction of APEs comprised thousands of substances, including adenosine in micromolar concentrations. Pollen-derived adenosine mediated A2 receptor-dependent induction of cAMP and inhibition of IL-12p70 in DCs. APEs digested with adenosine deaminase failed to mediate IL-12 inhibition. DCs of nonatopic donors exposed to APEs showed an adenosine-dependent reduced capacity to differentiate T(H)1 cells and an enhanced capacity to induce regulatory T cells and IL-10. DCs of atopic donors failed to induce IL-10 but instead induced IL-5 and IL-13. CONCLUSION: This study identifies adenosine out of thousands of metabolites as a potent immunoregulatory substance in pollen. It acts on the level of the DC, with differential effects in atopic and nonatopic donors.

Human mast cells express androgen receptors but treatment with testosterone exerts no influence on IgE-independent mast cell degranulation elicited by neuromuscular blocking agents.

Women predominate in the anaphylactic reactions to neuromuscular blocking agents (NMBA). The expression of oestrogen receptors has been demonstrated in mast cells and oestrogen treatment can enhance mast cell degranulation, but the influence of androgens remains largely unclear. Our immunocytochemical study showed the expression of androgen receptor (AR) in mast cells isolated from human foreskin as well as in two human mast cell lines, HMC-1 and LAD2. The amount of AR was most abundant in human skin mast cells as determined by real-time polymerase chain reaction analysis. Treatment of the HMC-1 mast cells with testosterone or 17beta-oestradiol, alone or in combination with different NMBA, did not affect mast cell degranulation as measured by the release of beta-hexosaminidase. Our study shows for the first time the expression of AR in human skin mast cells. Further studies using primary human mast cell cultures are needed to understand whether and how sex hormones can influence mast cell activation.