UVB Generates Microvesicle Particle Release in Part Due to Platelet‐activating Factor Signaling

Abstract

The lipid mediator platelet-activating factor (PAF) and oxidized glycerophosphocholine PAF agonists produced by ultraviolet B (UVB) have been demonstrated to play a pivotal role in UVB-mediated processes, from acute inflammation to delayed systemic immunosuppression. Recent studies have provided evidence that microvesicle particles (MVPs) are released from cells in response to various signals including stressors. Importantly, these small membrane fragments can interact with various cell types by delivering bioactive molecules. The present studies were designed to test if UVB radiation can generate MVP release from epithelial cells, and the potential role of PAF receptor (PAF-R) signaling in this process. We demonstrate that UVB irradiation of the human keratinocyte-derived cell line HaCaT resulted in the release of MVPs. Similarly, treatment of HaCaT cells with the PAF-R agonist carbamoyl PAF also generated equivalent amounts of MVP release. Of note, pretreatment of HaCaT cells with antioxidants blocked MVP release from UVB but not PAF-R agonist N-methyl carbamyl PAF (CPAF). Importantly, UVB irradiation of the PAF-R-negative human epithelial cell line KB and KB transduced with functional PAF-Rs resulted in MVP release only in PAF-R-positive cells. These studies demonstrate that UVB can generate MVPs in vitro and that PAF-R signaling appears important in this process.

UVB‐generated Microvesicle Particles: A Novel Pathway by Which a Skin‐specific Stimulus Could Exert Systemic Effects

“…Combining the previously published in vitro findings that UVB generates MVP (UVB‐MVP) in a process which involves the keratinocyte PAF‐R with the present ex vivo studies allows us to hypothesize that the keratinocyte PAF‐R could serve as an effector for UVB‐MVP release from human skin (Fig ). Several lines of evidence are supportive of the notion that activation of the PAF‐R mediates UVB‐MVP.…”

“…Second, the keratinocyte PAF‐R is linked to the same signal transduction pathways that have been implicated in MVP formation in other cell types . Finally, our previously published in vitro studies using PAF‐R‐positive KBP with PAF‐R‐negative KBM cells indicate that the PAF‐R is necessary for the formation of UVB‐MVP.…”

“…Four hours after treatment, fluid was removed from inside the blisters using a 30 ga needle on a 1‐mL syringe and weighed in tared tubes. After adjusting the volumes of the blister fluid to 500 μL with HBSS, MVP were isolated by differential centrifugation and quantified using a NanoSight NS300 instrument (NanoSight Ltd) as previously described . As depicted in Fig D, both UVB irradiation and topical CPAF induced increased levels of MVP formation in the blister fluid.…”

“…Recently, our group reported in this journal in vitro preliminary studies indicating that keratinocytes irradiated with UVB can induce the production of MVP . Using the human keratinocyte‐derived cell line HaCaT, we found that UVB generated MVP in a dose‐dependent manner, seen as early as one hour postirradiation.…”

Gemcitabine Induces Microvesicle Particle Release in a Platelet-Activating Factor-Receptor-Dependent Manner via Modulation of the MAPK Pathway in Pancreatic Cancer Cells

“…Growing evidence supports the crucial roles of microvesicle particles (MVPs), an extracellular vesicles in mediating the biological activities of cells in response to stimuli, including cancer therapy [12,13,14,15]. MVPs are small membrane-bound nanosized (10–100 nm) particles which are released by various cell types, including tumor cells, and contain a variety of bioactive substances, including lipids [14,15,16,17,18]. Thus, ongoing efforts are directed toward defining the functional role, as well as mechanisms of MVPs in disease pathophysiologies, including cancers, to devise better therapeutic strategies against these ailments.…”