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

Oyebanji, Oladayo A.; Brewer, Chad; Bayless, Sharlo; Schmeusser, Benjamin; Corbin, Danielle; Sulentic, Courtney E. W.; Sherwin, Catherine M.T.; Chen, Yanfang; Rapp, Christine M.; Cates, Elizabeth; Long, Yuhan; Travers, Jeffrey B.; Rohan, Craig A.

doi:10.1016/j.jid.2022.12.018

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…8,10,11 Shown in Figure 1A PAFR-independent. 14 Thermal burn injury at low levels is PAFRdependent but is PAFR-independent at higher levels of thermal burn injury. 11 As our previous studies have shown that IR is a potent stimulus for PAF agonist production, 5 our next studies tested the PAFR-dependency of IR-generated MVP.…”

Section: Radiation Therapy Produces Microvesicle Particle Release In ...mentioning

confidence: 99%

“…Indeed, MVPs have been shown to influence the release of cytokines that play a role in systemic and local inflammation as well as generating immunosuppression in response to agents as UVB and PDT. 8,14 Thus, understanding IR-mediated MVP formation may provide insights into possible pharmacological agents that can target this pathway, potentially preventing inflammatory and/or immunosuppressive responses associated with IR or RT. In particular, our studies indicate that IR generated MVP appears to be aSMase-dependent.…”

Section: Radiation Therapy Produces Microvesicle Particle Release In ...mentioning

confidence: 99%

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Radiation therapy produces microvesicle particle release in HaCaT keratinocytes

Torralba

Singh

Short

et al. 2023

Skin Research and Technology

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Section: Radiation Therapy Produces Microvesicle Particle Release In ...mentioning

confidence: 99%

Section: Radiation Therapy Produces Microvesicle Particle Release In ...mentioning

confidence: 99%

Radiation therapy produces microvesicle particle release in HaCaT keratinocytes

Torralba

Singh

Short

et al. 2023

Skin Research and Technology

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“…First, a global aSMase KO mouse ( Smpd1‐/‐ ) was used as per our previous reports using ultraviolet B radiation (UVB) or topical photodynamic therapy (PDT). 16 , 17 As shown in Figure 1 , ITBI resulted in decreased levels of elicitation reactions to DNFB in wild‐type C57BL6, which had no effect in aSMase‐deficient mice. Treatment of aSMase KO mice with the PAFR agonist CPAF resulted in an immunosuppressive effect as a positive control.…”

mentioning

confidence: 96%

Intoxicated thermal burn injury‐mediated systemic immunosuppression involves platelet‐activating factor and microvesicle particles

Lohade,

Rapp,

Henkels

et al. 2024

Skin Research and Technology

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Evidence that keratinocyte microvesicle particles carrying platelet-activating factor mediate the widespread multiorgan damage associated with intoxicated thermal burn injury

Lohade,

Brewer,

Rapp

et al. 2024

Journal of Leukocyte Biology

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Thermal burn injuries can result in significant morbidity and mortality. The combination of ethanol intoxication with thermal burn injury results in increased morbidity through an exaggerated inflammatory response involving many organs. Recent studies have linked involvement of the lipid mediator Platelet-activating factor (PAF) in the pathology associated with intoxicated thermal burn injury (ITBI). The present studies tested the roles of PAF and the elevated levels of subcellular microvesicle particles (MVP) generated in response to ITBI in the subsequent multi-organ toxicity. First, thermal burn injury of HaCaT keratinocytes preincubated with ethanol resulted in augmented MVP release, which was blocked by inhibiting the PAF-generating enzyme cytosolic phospholipase A2 and the PAF receptor (PAFR). Second, ITBI of mice resulted in increased pro-inflammatory cytokine production and neutrophilic inflammation in multiple organs which were not present in mice deficient in PAFRs nor the MVP-generating enzyme acid sphingomyelinase (aSMase). Moreover, the increased bacterial translocation from the gut to mesenteric lymph nodes previously reported in murine ITBI was also dependent upon PAFR and aSMase. MVP released from ITBI-treated keratinocytes contained high levels of PAFR agonistic activity. Finally, use of topical aSMase inhibitor imipramine following ITBI attenuated the widespread organ inflammatory response of ITBI, suggesting a potential therapeutic for this condition. These studies provide evidence for PAF-enriched MVP generated in skin, which then act upon the gut PAFR resulting in bacterial translocation as the mechanism for the multi-organ dysfunction associated with ITBI. Inasmuch as aSMase inhibitors are widely available, these studies could result in effective treatments for ITBI.

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

Cited by 5 publications

References 49 publications

Radiation therapy produces microvesicle particle release in HaCaT keratinocytes

Radiation therapy produces microvesicle particle release in HaCaT keratinocytes

Intoxicated thermal burn injury‐mediated systemic immunosuppression involves platelet‐activating factor and microvesicle particles

Evidence that keratinocyte microvesicle particles carrying platelet-activating factor mediate the widespread multiorgan damage associated with intoxicated thermal burn injury

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