258 research outputs found
Thermodiffusion of aqueous salt solutions: Hofmeister Series and overlapping hydration shells
No full textMotivationOur study of ionic solutes is motivated by the most important practical application of thermodiffusion, where it is used to monitor protein-ligand reactions. Proteins are complex molecules that contain ionic as well as non-ionic groups. While non-ionic solutes in water have been extensively studied recently (Niether and Wiegand, 2019), ionic solutes' concentration and temperature dependence have not been investigated systematically. For non-ionic compounds, a strong correlation between thermodiffusion and hydration was found (Niether and Wiegand, 2019). Figure 1: Schematic comparison of the temperature dependence of ST for non-ionic and ionic solutes at different concentrations: low (dotted line), intermediate (dashed line), and high (solid line).Comparison of non-ionic and ionic solutesWe found one striking difference between non-ionic and ionic solutes looking at the effect of concentration on the temperature dependence of the Soret coefficient S_T, as illustrated in Fig. 1 (Mohanakumar et al. 2021). For a typical non-ionic solute in water, the behavior of ST changes from increasing with temperature to decreasing with temperature as the concentration increases. This is correlated with the hydration of the solutes which decreases as the concentration increases. Only very hydrophilic non-ionic solutes have ST values that increase with temperature for all concentrations. In contrast, the Soret coefficients of ionic solutes show the typical temperature dependence of very hydrophilic solutes over the entire concentration range. For salts with a high degree of dissociation we might have a tightly bound first hydration layer, which leads to a highly hydrophilic entity. For less dissociated salts it might be explained by cluster formation of the salts with increasing concentrations. Even at high salt concentrations the clusters as a whole are hydrated at their surfaces by water, but the total exposure to water is less as the surface decreases when more ions are part of larger clusters. Figure 2: (a) SiT values of all studied systems plotted as functionof log P. Note, that log P is the sum of an ionic and non-ionic contribution. First order polynomials of concentration and temperature have been used to fit the data using Eq.1. (b) Sequence of the anions based on SiT for the two investigated cations in comparison with the Hofmeister series.Anion and Cation influence on ST We investigated systematically the concentration and temperature dependence of the thermodiffusion of aqueous solutions of various potassium and sodium salts (Mohanakumar et al. 2021, Mohanakumar et al. 2022a). To describe the temperature and concentration dependence we used an empirical Ansatz suggested by Wittko and Köhler (Wittko and Köhler, 2007)S_T\left(m,T\right)=\alpha\left(m\right)\beta\left(T\right)+S_T^i (1)With polynomial serial expansions for \alpha\left(m\right) and \beta\left(T\right)\alpha\left(m\right)=\alpha_1m+\alpha_2m^2+\alpha_3m^3+\cdots\bigm\beta\left(m\right)=1+b_1\left(T-T_0\right)+b_2\left(T-T_0\right)^2+\cdots (2) m is the molality, T_0 is an arbitrary reference temperature, set to T_0=25°C and S_T^i is a temperature and concentration independent constant. Note, that we set a_0=0 as it is strongly coupled to S_T^i. We could describe the temperature and concentration dependence of S_T of various potassium and sodium salts in water using Eq.(1). In Figure 2(a) we display the adjustable parameter S_T^i as function of\ \log{P}, with P being the ratio of the equilibrium concentration of the solute (salt) in octanol and in water. So, a negative \log{P} signifies stronger hydrophilicity. We find for all investigated salts a linear correlation between S_T^i and\log{P}. This implies that also, for ionic solutes, hydrophilicity plays an important role. If we compare with the hydrophilicity scale of the Hofmeister series, we find a good agreement except for the thiocyanate anion, which should be, according to Hofmeister, the most hydrophobic anion. In brief, we can state that the hydration of the ions plays a significant role.Overlapping hydration shellsVarious salts in water exhibit non-monotonic variations of the Soret coefficient S_T with concentration, which is not understood on a microscopic level. We investigated the thermodiffusive properties of aqueous solutions of sodium iodide, potassium iodide and lithium iodide, using thermal diffusion forced Rayleigh scattering in a concentration range of 0.5 – 4 mole per kg of solvent and a temperature range of 15 to 45°C (Mohanakumar et al. 2022b). In all three cases S_T has a minimum at m_{min}=1 mole per kg of solvent. We develop an intuitive picture in which the relevant objects are the fully hydrated salt molecules (FHP), including all water molecules that behave differently from bulk water. Our hypothesis is that these FHPs form a random close packing at m_{min}, which implies that the outer hydration shell start to touch as indicated in Figure 3. Preliminary, somewhat sketchy calculations indicate that indeed Soret coefficients begin to rise beyond m_{min}. Indications are given as to why the model will fail at large concentrations. Figure 3: Hydrated salt molecules overlapping with increasing concentration. The green–red sphere represents the bare salt molecule, after adding the blue shell of strongly attached water molecules we get the salt particle (HSP), while after adding next the outer light blue shell of perturbed water we arrive at the hydrated salt molecule, called FHP. At concentrations above mmin the outer shells overlap as shown on the right side.ConclusionsWe have studied the thermophoretic properties of various salts in water over a range of temperatures and concentrations. Although the temperature dependence of the Soret coefficient of the ionic compounds does not change in the same pronounced way as function of their hydrophilicity observed for non-ionic solutes, we find a linear correlation between S_T^i and \log{P}. Most likely, the hydration shell of ionic solutes is more tightly bound to the ions than in the case of non-ionic solutes, so we find a similar temperature dependence of the Soret coefficient for all concentrations. Additionally, overlapping of the hydration shells might also be responsible for the occurrence of a minimum of S_T with concentration. However, this hypothesis needs to be quantified by computer simulations. AcknowledgementsWe thank Fernando Bresme, Jan Dhont and Jutta Luettmer-Strathmann for fruitful and helpful discussions. ReferencesD. Niether, S. Wiegand, Thermophoresis of biological and biocompatible compounds in aqueous solution, J. Phys. Condens. Matter, 31, 503003 (2019).S. Mohanakumar, J. Luettmer-Strathmann, S. Wiegand, Thermodiffusion of aqueous solutions of various potassium salts, J. Chem. Phys., 154, 84506 (2021).S. Mohanakumar, S. Wiegand: Towards understanding specific ion effects in aqueous media using thermodiffusion The Eur. Phys. J. E 45(2), 10 (2022a).G. Wittko, W. Köhler, On the temperature dependence of thermal diffusion of liquid mixtures, Europhys. Lett. 78, 46007 (2007).S. Mohanakumar, H. Kriegs, W. J. Briels, S. Wiegand, Overlapping hydration shells in salt solutions causing non-monotonic Soret coefficients with varying concentration PCCP 24, 27380 (2022b)
Cutting Edge: Pseudomonas aeruginosa Abolishes Established Lung Transplant Tolerance by Stimulating B7 Expression on Neutrophils
No full textThe mechanisms that link bacterial infection to solid organ rejection remain unclear. In this study, we show that following the establishment of lung allograft acceptance in mice, Pseudomonas aeruginosa airway infection induces a G-CSF-dependent neutrophilia that stimulates acute rejection. Graft-infiltrating neutrophils sharply upregulate the B7 molecules CD80 and CD86, but they do not express CD40 or MHC class II in response to P. aeruginosa infection. Neutrophil B7 promotes naive CD4(+) T cell activation and intragraft IL-2(+), IFN-gamma(+), and IL-17(+) T lymphocyte accumulation. Intravital two-photon microscopy reveals direct interactions between neutrophils and CD4(+) T cells within pulmonary allografts. Importantly, lung rejection in P. aeruginosa-infected recipients is triggered by CD80/86 on neutrophils and can be prevented by B7 blockade without affecting clearance of this pathogen. These data show that neutrophils enhance T cell activation through B7 trans-costimulation and suggest that inhibiting neutrophil-mediated alloimmunity can be accomplished without compromising bacterial immune surveillance. The Journal of Immunology, 2012, 189: 4221-4225
In Vivo Generation of Hydroxyl Radicals and MPTP-Induced Dopaminergic Toxicity in the Basal Ganglia
No full textImmune Responses to Tissue-Restricted Nonmajor Histocompatibility Complex Antigens in Allograft Rejection
No full textChronic diseases that result in end-stage organ damage cause inflammation, which can reveal sequestered self-antigens (SAgs) in that organ and trigger autoimmunity. The thymus gland deletes self-reactive T-cells against ubiquitously expressed SAgs, while regulatory mechanisms in the periphery control immune responses to tissue-restricted SAgs. It is now established that T-cells reactive to SAgs present in certain organs (e.g., lungs, pancreas, and intestine) are incompletely eliminated, and the dysregulation of peripheral immuneregulation can generate immune responses to SAgs. Therefore, chronic diseases can activate self-reactive lymphocytes, inducing tissue-restricted autoimmunity. During organ transplantation, donor lymphocytes are tested against recipient serum (i.e., cross-matching) to detect antibodies (Abs) against donor human leukocyte antigens, which has been shown to reduce Ab-mediated hyperacute rejection. However, primary allograft dysfunction and rejection still occur frequently. Because donor lymphocytes do not express tissue-restricted SAgs, preexisting Abs against SAgs are undetectable during conventional cross-matching. Preexisting and de novo immune responses to tissue-restricted SAgs (i.e., autoimmunity) play a major role in rejection. In this review, we discuss the evidence that supports autoimmunity as a contributor to rejection. Testing for preexisting and de novo immune responses to tissue-restricted SAgs and treatment based on immune responses after organ transplantation may improve short- and long-term outcomes after transplantation
Dissociation of autologous and allogeneic mixed lymphocyte reactivity by using a monoclonal antibody specific for human t helper cells.
No full textNeutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance
Get PDFNeutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse-1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2-photon microscopy, we analyzed the effects of DNAse-1 on NETs in mouse orthotopic lung allografts damaged by ischemia-reperfusion injury. Although DNAse-1 treatment rapidly degrades intragraft NETs, the consequential release of NET fragments induces prolonged interactions between infiltrating CD4 + T cells and donor-derived antigen presenting cells. DNAse-1 generated NET fragments also promote human alveolar macrophage inflammatory cytokine production and prime dendritic cells for alloantigen-specific CD4 + T cell proliferation through activating toll-like receptor (TLR) — Myeloid Differentiation Primary Response 88 (MyD88) signaling pathways. Furthermore, and in contrast to allograft recipients with a deficiency in NET generation due to a neutrophil-specific ablation of Protein Arginine Deiminase 4 (PAD4), DNAse-1 administration to wild-type recipients promotes the recognition of allo- and self-antigens and prevents immunosuppression-mediated lung allograft acceptance through a MyD88-dependent pathway. Taken together, these data show that the rapid catalytic release of NET fragments promotes innate immune responses that prevent lung transplant tolerance. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeon
Definition of the T Cell-Mediated Immune Response to Mammaglobin, a Novel Breast Cancer-Associated Protein
No full textDefinition of the T Cell-Mediated Immune Response to Mammaglobin, a Novel Breast Cancer-Associated Protein
No full textDefinition of the T Cell-Mediated Immune Response to Mammaglobin, a Novel Breast Cancer-Associated Protein
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