12 research outputs found
Protein Cross-Linking and Oligomerization through Dityrosine Formation upon Exposure to Ozone
Water uptake of subpollen aerosol particles: Hygroscopic growth, cloud condensation nuclei activation, and liquid-liquid phase separation
Pollen grains emitted from vegetation can release subpollen particles (SPPs) that contribute to the fine fraction of atmospheric aerosols and may act as cloud condensation nuclei (CCN), ice nuclei (IN), or aeroallergens. Here, we investigate and characterize the hygroscopic growth and CCN activation of birch, pine, and rapeseed SPPs. A high-humidity tandem differential mobility analyzer (HHTDMA) was used to measure particle restructuring and water uptake over a wide range of relative humidity (RH) from 2â% to 99.5â%, and a continuous flow CCN counter was used for size-resolved measurements of CCN activation at supersaturations (S) in the range of 0.2â% to 1.2â%. For both subsaturated and supersaturated conditions, effective hygroscopicity parameters, Îș, were obtained by Köhler model calculations. Gravimetric and chemical analyses, electron microscopy, and dynamic light scattering measurements were performed to characterize further properties of SPPs from aqueous pollen extracts such as chemical composition (starch, proteins, DNA, and inorganic ions) and the hydrodynamic size distribution of water-insoluble material. All investigated SPP samples exhibited a sharp increase of water uptake and Îș above âŒ95â% RH, suggesting a liquidâliquid phase separation (LLPS). The HHTDMA measurements at RHâ>95â% enable closure between the CCN activation at water vapor supersaturation and hygroscopic growth at subsaturated conditions, which is often not achieved when hygroscopicity tandem differential mobility analyzer (HTDMA) measurements are performed at lower RH where the water uptake and effective hygroscopicity may be limited by the effects of LLPS. Such effects may be important not only for closure between hygroscopic growth and CCN activation but also for the chemical reactivity, allergenic potential, and related health effects of SPPs
Nitration of Wheat Amylase Trypsin Inhibitors Increases Their Innate and Adaptive Immunostimulatory Potential in vitro
Amylase trypsin inhibitors (ATI) can be found in all gluten containing cereals and are, therefore, ingredient of basic foods like bread or pasta. In the gut ATI can mediate innate immunity via activation of the Toll-like receptor 4 (TLR4) on immune cells residing in the lamina propria, promoting intestinal, as well as extra-intestinal, inflammation. Inflammatory conditions can induce formation of peroxynitrite (ONOOâ) and, thereby, endogenous protein nitration in the body. Moreover, air pollutants like ozone (O3) and nitrogen dioxide (NO2) can cause exogenous protein nitration in the environment. Both reaction pathways may lead to the nitration of ATI. To investigate if and how nitration modulates the immunostimulatory properties of ATI, they were chemically modified by three different methods simulating endogenous and exogenous protein nitration and tested in vitro. Here we show that ATI nitration was achieved by all three methods and lead to increased immune reactions. We found that ATI nitrated by tetranitromethane (TNM) or ONOOâ lead to a significantly enhanced TLR4 activation. Furthermore, in human primary immune cells, TNM nitrated ATI induced a significantly higher T cell proliferation and release of Th1 and Th2 cytokines compared to unmodified ATI. Our findings implicate a causative chain between nitration, enhanced TLR4 stimulation, and adaptive immune responses, providing major implications for public health, as nitrated ATI may strongly promote inhalative wheat allergies (baker's asthma), non-celiac wheat sensitivity (NCWS), other allergies, and autoimmune diseases. This underlines the importance of future work analyzing the relationship between endo- and exogenous protein nitration, and the rise in incidence of ATI-related and other food hypersensitivities
Nitration of the Birch Pollen Allergen Bet v 1.0101: Efficiency and Site-Selectivity of Liquid and Gaseous Nitrating Agents
Recommended from our members
Protein Cross-Linking and Oligomerization through Dityrosine Formation upon Exposure to Ozone.
Air pollution is a potential driver for the increasing prevalence of allergic disease, and post-translational modification by air pollutants can enhance the allergenic potential of proteins. Here, the kinetics and mechanism of protein oligomerization upon ozone (O3) exposure were studied in coated-wall flow tube experiments at environmentally relevant O3 concentrations, relative humidities and protein phase states (amorphous solid, semisolid, and liquid). We observed the formation of protein dimers, trimers, and higher oligomers, and attribute the cross-linking to the formation of covalent intermolecular dityrosine species. The oligomerization proceeds fast on the surface of protein films. In the bulk material, reaction rates are limited by diffusion depending on phase state and humidity. From the experimental data, we derive a chemical mechanism and rate equations for a kinetic multilayer model of surface and bulk reaction enabling the prediction of oligomer formation. Increasing levels of tropospheric O3 in the Anthropocene may promote the formation of protein oligomers with enhanced allergenicity and may thus contribute to the increasing prevalence of allergies
Protein Cross-Linking and Oligomerization through Dityrosine Formation upon Exposure to Ozone
Air pollution is a potential driver
for the increasing prevalence
of allergic disease, and post-translational modification by air pollutants
can enhance the allergenic potential of proteins. Here, the kinetics
and mechanism of protein oligomerization upon ozone (O<sub>3</sub>) exposure were studied in coated-wall flow tube experiments at environmentally
relevant O<sub>3</sub> concentrations, relative humidities and protein
phase states (amorphous solid, semisolid, and liquid). We observed
the formation of protein dimers, trimers, and higher oligomers, and
attribute the cross-linking to the formation of covalent intermolecular
dityrosine species. The oligomerization proceeds fast on the surface
of protein films. In the bulk material, reaction rates are limited
by diffusion depending on phase state and humidity. From the experimental
data, we derive a chemical mechanism and rate equations for a kinetic
multilayer model of surface and bulk reaction enabling the prediction
of oligomer formation. Increasing levels of tropospheric O<sub>3</sub> in the Anthropocene may promote the formation of protein oligomers
with enhanced allergenicity and may thus contribute to the increasing
prevalence of allergies
Recommended from our members
Nitration of the birch pollen allergen Bet v 1.0101: efficiency and site-selectivity of liquid and gaseous nitrating agents.
Nitration of the major birch pollen allergen Bet v 1 alters the immune responses toward this protein, but the underlying chemical mechanisms are not yet understood. Here we address the efficiency and site-selectivity of the nitration reaction of recombinant protein samples of Bet v 1.0101 with different nitrating agents relevant for laboratory investigations (tetranitromethane, TNM), for physiological processes (peroxynitrite, ONOO(-)), and for the health effects of environmental pollutants (nitrogen dioxide and ozone, Oâ/NOâ). We determined the total tyrosine nitration degrees (ND) and the NDs of individual tyrosine residues (NDY). High-performance liquid chromatography coupled to diode array detection and HPLC coupled to high-resolution mass spectrometry analysis of intact proteins, HPLC coupled to tandem mass spectrometry analysis of tryptic peptides, and amino acid analysis of hydrolyzed samples were performed. The preferred reaction sites were tyrosine residues at the following positions in the polypeptide chain: Y83 and Y81 for TNM, Y150 for ONOO(-), and Y83 and Y158 for Oâ/NOâ. The tyrosine residues Y83 and Y81 are located in a hydrophobic cavity, while Y150 and Y158 are located in solvent-accessible and flexible structures of the C-terminal region. The heterogeneous reaction with Oâ/NOâ was found to be strongly dependent on the phase state of the protein. Nitration rates were about one order of magnitude higher for aqueous protein solutions (âŒ20% per day) than for protein filter samples (âŒ2% per day). Overall, our findings show that the kinetics and site-selectivity of nitration strongly depend on the nitrating agent and reaction conditions, which may also affect the biological function and adverse health effects of the nitrated protein
Nitration of the Birch Pollen Allergen Bet v 1.0101: Efficiency and Site-Selectivity of Liquid and Gaseous Nitrating Agents
Nitration
of the major birch pollen allergen Bet v 1 alters the
immune responses toward this protein, but the underlying chemical
mechanisms are not yet understood. Here we address the efficiency
and site-selectivity of the nitration reaction of recombinant protein
samples of Bet v 1.0101 with different nitrating agents relevant for
laboratory investigations (tetranitromethane, TNM), for physiological
processes (peroxynitrite, ONOO<sup>â</sup>), and for the health
effects of environmental pollutants (nitrogen dioxide and ozone, O<sub>3</sub>/NO<sub>2</sub>). We determined the total tyrosine nitration
degrees (ND) and the NDs of individual tyrosine residues (ND<sub>Y</sub>). High-performance liquid chromatography coupled to diode array
detection and HPLC coupled to high-resolution mass spectrometry analysis
of intact proteins, HPLC coupled to tandem mass spectrometry analysis
of tryptic peptides, and amino acid analysis of hydrolyzed samples
were performed. The preferred reaction sites were tyrosine residues
at the following positions in the polypeptide chain: Y83 and Y81 for
TNM, Y150 for ONOO<sup>â</sup>, and Y83 and Y158 for O<sub>3</sub>/NO<sub>2</sub>. The tyrosine residues Y83 and Y81 are located
in a hydrophobic cavity, while Y150 and Y158 are located in solvent-accessible
and flexible structures of the C-terminal region. The heterogeneous
reaction with O<sub>3</sub>/NO<sub>2</sub> was found to be strongly
dependent on the phase state of the protein. Nitration rates were
about one order of magnitude higher for aqueous protein solutions
(âŒ20% per day) than for protein filter samples (âŒ2%
per day). Overall, our findings show that the kinetics and site-selectivity
of nitration strongly depend on the nitrating agent and reaction conditions,
which may also affect the biological function and adverse health effects
of the nitrated protein
Recommended from our members
Air Pollution and Climate Change Effects on Allergies in the Anthropocene: Abundance, Interaction, and Modification of Allergens and Adjuvants.
Air pollution and climate change are potential drivers for the increasing burden of allergic diseases. The molecular mechanisms by which air pollutants and climate parameters may influence allergic diseases, however, are complex and elusive. This article provides an overview of physical, chemical and biological interactions between air pollution, climate change, allergens, adjuvants and the immune system, addressing how these interactions may promote the development of allergies. We reviewed and synthesized key findings from atmospheric, climate, and biomedical research. The current state of knowledge, open questions, and future research perspectives are outlined and discussed. The Anthropocene, as the present era of globally pervasive anthropogenic influence on planet Earth and, thus, on the human environment, is characterized by a strong increase of carbon dioxide, ozone, nitrogen oxides, and combustion- or traffic-related particulate matter in the atmosphere. These environmental factors can enhance the abundance and induce chemical modifications of allergens, increase oxidative stress in the human body, and skew the immune system toward allergic reactions. In particular, air pollutants can act as adjuvants and alter the immunogenicity of allergenic proteins, while climate change affects the atmospheric abundance and human exposure to bioaerosols and aeroallergens. To fully understand and effectively mitigate the adverse effects of air pollution and climate change on allergic diseases, several challenges remain to be resolved. Among these are the identification and quantification of immunochemical reaction pathways involving allergens and adjuvants under relevant environmental and physiological conditions
Air Pollution and Climate Change Effects on Allergies in the Anthropocene: Abundance, Interaction, and Modification of Allergens and Adjuvants
Air pollution and climate change are potential drivers for the increasing burden of allergic diseases. The molecular mechanisms by which air pollutants and climate parameters may influence allergic diseases, however, are complex and elusive. This article provides an overview of physical, chemical and biological interactions between air pollution, climate change, allergens, adjuvants and the immune system, addressing how these interactions may promote the development of allergies. We reviewed and synthesized key findings from atmospheric, climate, and biomedical research. The current state of knowledge, open questions, and future research perspectives are outlined and discussed. The Anthropocene, as the present era of globally pervasive anthropogenic influence on planet Earth and, thus, on the human environment, is characterized by a strong increase of carbon dioxide, ozone, nitrogen oxides, and combustion- or traffic-related particulate matter in the atmosphere. These environmental factors can enhance the abundance and induce chemical modifications of allergens, increase oxidative stress in the human body, and skew the immune system toward allergic reactions. In particular, air pollutants can act as adjuvants and alter the immunogenicity of allergenic proteins, while climate change affects the atmospheric abundance and human exposure to bioaerosols and aeroallergens. To fully understand and effectively mitigate the adverse effects of air pollution and climate change on allergic diseases, several challenges remain to be resolved. Among these are the identification and quantification of immunochemical reaction pathways involving allergens and adjuvants under relevant environmental and physiological conditions