In psoriasis, IFN-α–stimulated mast cells release exosomes containing cytoplasmic PLA2 that are transferred to CD1a-expressing cells and generate neolipid antigens which induce the production of IL-22 and IL-17A by CD1a-reactive T cells.
Atopic dermatitis is a common pruritic skin disease in which barrier dysfunction and cutaneous inflammation play a role in pathogenesis. Mechanisms underlying the associated inflammation are not fully understood, and while CD1a-expressing Langerhans cells are known to be enriched within lesions, their role in clinical disease pathogenesis has not been studied. Here we observed that house dust mite (HDM) generates neolipid antigens for presentation by CD1a to T cells in the blood and skin lesions of affected individuals. HDM-responsive CD1a-reactive T cells increased in frequency after birth and showed rapid effector function, consistent with antigen-driven maturation. To define the underlying mechanisms, we analyzed HDM-challenged human skin and observed allergen-derived phospholipase (PLA2) activity in vivo. CD1a-reactive T cell activation was dependent on HDM-derived PLA2 and such cells infiltrated the skin after allergen challenge. Filaggrin insufficiency is associated with atopic dermatitis, and we observed that filaggrin inhibits PLA2 activity and inhibits CD1a-reactive PLA2-generated neolipid-specific T cell activity from skin and blood. The most widely used classification schemes of hypersensitivity, such as Gell and Coombs are predicated on the idea that non-peptide stimulants of T cells act as haptens that modify peptides or proteins. However our results point to a broader model that does not posit haptenation, but instead shows that HDM proteins generate neolipid antigens which directly activate T cells. Specifically, the data identify a pathway of atopic skin inflammation, in which house dust mite-derived phospholipase A2 generates antigenic neolipids for presentation to CD1a-reactive T cells, and define PLA2 inhibition as a function of filaggrin, supporting PLA2 inhibition as a therapeutic approach.
During the 2009–2010 A/H1N1 influenza pandemic, pregnant women infected with the virus experienced excess morbidity and mortality when compared with other groups. Once a vaccine was available, pregnant women were a priority group for vaccination. Only a few studies have reported on the uptake of 2009 A/H1N1 influenza vaccine among pregnant women during the pandemic and none were from Asia. The purpose of this study was to examine factors associated with 2009 A/H1N1 influenza vaccine uptake among pregnant women in Hong Kong. Using a multi-center, cross-sectional design, we recruited 549 postpartum women from four post-natal wards in Hong Kong over a 4-month period during the second wave of the A/H1N1 influenza pandemic in the winter and spring of 2010. Only 6.2% (n = 34) of participants had received the 2009 A/H1N1 influenza vaccine and 4.9% (n = 27) had received the seasonal influenza vaccine. The most common reasons for not receiving the 2009 A/H1N1 vaccine were fear of causing harm to themselves or their fetus. A high knowledge level (OR = 19.06; 95% CI 5.55, 65.48), more positive attitudes (OR = 3.52; 95% CI 1.37, 9.07), and having a family member who had the 2009 A/H1N1 influenza vaccine (OR = 7.69; 95% CI 2.92, 20.19) were independently and positively associated with vaccination. Study results show an unacceptably low uptake of the pandemic A/H1N1 influenza vaccine among pregnant women in Hong Kong. Interventions to increase influenza vaccine knowledge and uptake among this group should be a priority for future pandemic planning and seasonal vaccination campaigns.
Polyphyllin D (PD) is a potent anticancer agent isolated from a traditional medicinal herb Paris polyphylla that has been used in China for many years to treat cancer. PD is not a substrate of p-glycoprotein, and it can bypass the multi-drug resistance in cancer cell line R-HepG2. However, the effect of PD on the induction of cell death in human erythrocytes remains unknown. Given that PD is a small molecule that can depolarize the mitochondrial membrane potential and release apoptosis-inducing factor (AIF) in isolated mitochondria, we hypothesized that the apoptogenic effect of PD in human erythrocytes devoid of mitochondria would be minimal. This study therefore tried to evaluate the in vitro effect of PD on hemolysis and apoptosis in human erythrocytes. Apoptosis in human red blood cells (RBCs), also known as eryptosis or erythroptosis, after PD treatment was determined by flow cytometry and confocal microscopy for the phosphatidyl-serine externalization and other apoptosis feature events. False to our prediction, PD caused hemolysis and eryptosis/erythroptosis in human RBCs. Mechanistically, elevation in the cytosolic Ca²⁺ ion level seems to be a key but not the only mediator in the PD-mediated eryptosis/erythroptosis because depletion of the external Ca²⁺ could not eliminate the PD effect. Also, PD was able to permeabilize the membrane of RBC ghosts in a way similar to digitonin. Taken together, we report here for the first time the toxicity of PD in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis/erythroptosis.
The effect of CTAB (cetyltrimethylammonium bromide)- or PEG (polyethylene glycol)-coated gold-nanorods (Au-NRs) on the non-IgE mediated allergic response was studied. We found that the CTAB-Au-NRs released more allergic mediators such as histamine and β-hexosaminidase from human basophil KU812, a common model for studying allergy, after 20 min incubation. Also, the CTAB-Au-NRs induced more apoptosis than the PEG-Au-NRs in KU812 24 h after treatment. These short- and long-term effects were not solely due to the CTAB residues in the supernatant desorbed from the Au-NRs.
Defects introduced into electroplated Cu films during room-temperature recrystallization probed by a monoenergetic positron beam J. Appl. Phys. 98, 043504 (2005); 10.1063/1.2009813 Studies of the driving force for room-temperature microstructure evolution in electroplated copper films Vacancy-type defects in electroplated Cu films probed by using a monoenergetic positron beam J. Appl. Phys. 95, 913 (2004); 10.1063/1.1635648Seed layer dependence of room-temperature recrystallization in electroplated copper films
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