Acute ethanol exposure stimulates microvesicle particle generation in keratinocytes

Awoyemi, Azeezat A; Borchers, Christina E.; Liu, Langni; Chen, Yanfang; Rapp, Christine M.; Brewer, Chad; Elased, Ramzi; Travers, Jeffrey B.

doi:10.1016/j.toxlet.2021.11.008

Cited by 5 publications

(5 citation statements)

References 38 publications

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“…Additionally, immunosuppression has been found to be exacerbated by ethanol and TBI combination injury, where T‐cell and dendrite cell counts were decreased by the ethanol exposure in rats 44 . Additionally, another study which confirms the increase in MVP levels due to ethanol exposure and intoxicated TBI, found that imipramine is also effective at decreasing MVP levels solely due to ethanol exposure, not just in the case of the combination injuries 16 . This indicates there is involvement of aSMase in MVP generation due to ethanol.…”

Section: Mvps and Itbimentioning

confidence: 91%

“…44 Additionally, another study which confirms the increase in MVP levels due to ethanol exposure and intoxicated TBI, found that imipramine is also effective at decreasing MVP levels solely due to ethanol exposure, not just in the case of the combination injuries. 16 This indicates there is involvement of aSMase in MVP generation due to ethanol.…”

Section: Mvps and Itbimentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

“…As will detail in this review, recent studies have provided new insights into how the combination of ethanol and TBI can result in the above acute and delayed pathologic effects. 15,16 These have implicated a potent lipid mediator and subcellular particle formation. Finally, this new unified theory for ITBI pathology has therapeutic implications in the treatment of the unfortunate patient.…”

Section: Introductionmentioning

confidence: 99%

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Platelet‐activating factor and microvesicle particles as potential mediators for the toxicity associated with intoxicated thermal burn injury

et al. 2022

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Thermal burn injuries (TBIs) in patients who are alcohol-intoxicated result in greater morbidity and mortality. The systemic toxicity found in human patients, which includes both immediate systemic cytokine generation with multiple organ failure and a delayed systemic immunosuppression, has previously been replicated in mouse models combining ethanol and localized TBI. Though considerable insights have been provided with these models, the exact mechanisms for these pathologic effects are unclear. In this review, we highlight the roles of the lipid mediator platelet-activating factor (PAF) and subcellular microvesicle particle (MVP) release in response to intoxicated thermal burn injury (ITBI) as effectors in the pathology. Particularly, MVP is released from keratinocytes in response to PAF receptor (PAFR) activation due to excess PAF produced by ITBI. These subcellular particles carry and thus protect the metabolically labile PAF which enable binding of this potent lipid mediator to several key sites. We hypothesize that PAF carried by MVP can bind to PAFR within the gut, activating myosin light chain kinase (MLCK). The subsequent gut barrier dysfunction in response to MLCK activation then allows bacteria to invade the lymphatic system and, eventually, the bloodstream, resulting in sepsis and resultant dysregulated inflammation in multiple organs. PAF in MVP also activate the skin mast cell PAFR resulting in migration of this key effector cell to the lymph nodes to induce immunosuppression. This review thus provides a mechanism and potential therapeutic approaches for the increased toxicity and immunosuppressive outcomes of TBI in the presence of acute ethanol exposure.

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Section: Mvps and Itbimentioning

confidence: 91%

Section: Mvps and Itbimentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Platelet‐activating factor and microvesicle particles as potential mediators for the toxicity associated with intoxicated thermal burn injury

et al. 2022

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“…Both MVPs and PAF are released due to activation of PAFR. In fact, MVP production and activation can be triggered by a great variety of mechanisms, including acute alcohol poisoning (35,82).…”

Section: Microvesicle Particlesmentioning

confidence: 99%

UVB-Induced Microvesicle Particle Release and Its Effects on the Cutaneous Microenvironment

et al. 2022

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Ultraviolet B radiation (UVB) has profound effects on human skin that results in a broad spectrum of immunological local and systemic responses and is the major cause of skin carcinogenesis. One important area of study in photobiology is how UVB is translated into effector signals. As the skin is exposed to UVB light, subcellular microvesicle particles (MVP), a subtype of bioactive extracellular vesicles, are released causing a variety of local and systemic immunological effects. In this review, we highlight keratinocyte MVP release in keratinocytes in response to UVB. Specifically, Platelet-activating factor receptor agonists generated by UVB result in MVP released from keratinocytes. The downstream effects of MVP release include the ability of these subcellular particles to transport agents including the glycerophosphocholine-derived lipid mediator Platelet-activating factor (PAF). Moreover, even though UVB is only absorbed in the epidermis, it appears that PAF release from MVPs also mediates systemic immunosuppression and enhances tumor growth and metastasis. Tumor cells expressing PAF receptors can use this mechanism to evade chemotherapy responses, leading to treatment resistance for advanced cancers such as melanoma. Furthermore, novel pharmacological agents provide greater insight into the UVB-induced immune response pathway and a potential target for pharmacological intervention. This review outlines the need to more clearly elucidate the mechanism linking UVB-irradiation with the cutaneous immune response and its pathological manifestations. An improved understanding of this process can result in new insights and treatment strategies for UVB-related disorders from carcinogenesis to photosensitivity.

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Topical Photodynamic Therapy Generates Bioactive Microvesicle Particles: Evidence for a Pathway Involved in Immunosuppressive Effects

Oyebanji

Brewer

Bayless

et al. 2023

Journal of Investigative Dermatology

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Acute ethanol exposure stimulates microvesicle particle generation in keratinocytes

Cited by 5 publications

References 38 publications

Platelet‐activating factor and microvesicle particles as potential mediators for the toxicity associated with intoxicated thermal burn injury

Platelet‐activating factor and microvesicle particles as potential mediators for the toxicity associated with intoxicated thermal burn injury

UVB-Induced Microvesicle Particle Release and Its Effects on the Cutaneous Microenvironment

Topical Photodynamic Therapy Generates Bioactive Microvesicle Particles: Evidence for a Pathway Involved in Immunosuppressive Effects

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