ABSTRACT
A complete carcinogen, ultraviolet B (UVB) radiation (290-320 nm), is the major cause of skin cancer. UVB-induced systemic immunosuppression that contributes to photocarcinogenesis is due to the glycerophosphocholine-derived lipid mediator platelet-activating factor (PAF). A major question in photobiology is how UVB radiation, which only absorbs appreciably in the epidermal layers of skin, can generate systemic effects. UVB exposure and PAF receptor (PAFR) activation in keratinocytes induce the release of large numbers of microvesicle particles (MVPs; extracellular vesicles ranging from 100 to 1000 nm in size). MVPs released from skin keratinocytes in vitro in response to UVB (UVB-MVPs) are dependent on the keratinocyte PAFR. Here, we used both pharmacologic and genetic approaches in cells and mice to show that both the PAFR and enzyme acid sphingomyelinase (aSMase) were necessary for UVB-MVP generation. Our discovery that the calcium-sensing receptor is a keratinocyte-selective MVP marker allowed us to determine that UVB-MVPs leaving the keratinocyte can be found systemically in mice and humans following UVB exposure. Moreover, we found that UVB-MVPs contained bioactive contents including PAFR agonists that allowed them to serve as effectors for UVB downstream effects, in particular UVB-mediated systemic immunosuppression.
Subject(s)
Cell-Derived Microparticles/immunology , Immune Tolerance/radiation effects , Keratinocytes/immunology , Ultraviolet Rays , Animals , Cell Line , Cell-Derived Microparticles/genetics , Female , Humans , Mice , Mice, Knockout , Platelet Activating Factor/genetics , Platelet Activating Factor/immunology , Platelet Membrane Glycoproteins/genetics , Platelet Membrane Glycoproteins/immunology , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/immunology , Sphingomyelin Phosphodiesterase/genetics , Sphingomyelin Phosphodiesterase/immunologyABSTRACT
Thermal burn injuries are common and are associated with physical and psychologic repercussions. For epileptic patients, the risk for environmental injuries is remarkably higher. We present 2 cases of thermal burn injuries following nocturnal seizures. Many epileptic patients are educated on ways to prevent injury; however, these safety precautions tend to focus primarily on daytime activities. We highlight the potential presentation and impacts of the thermal lesions. In addition, we offer suggestions for improvements in patient education and injury prevention.
