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The photosensitivity associated with deficiency of xeroderma pigmentosum type A (XPA) has been previously shown to be associated with excess levels of the lipid mediator platelet\u2010activating factor (PAF) generated by the keratinocyte. As PAF has been reported to trigger the production of subcellular microvesicle particles (MVP) due to the enzyme acid sphingomyelinase (aSMase), the goal of these studies was to discern if PAF and aSMase could serve as therapeutic targets for the XPA deficiency photosensitivity. HaCaT keratinocytes lacking XPA generated greater levels of MVP in comparison to control cells. Mice deficient in XPA also generated enhanced MVP levels in skin and in plasma in response to UV radiation. Use of a genetic strategy with mice deficient in both XPA and PAF receptors revealed that these mice generated less MVP release as well as decreased skin erythema and cytokine release compared to XPA knockout mice alone. Finally, the aSMase inhibitor imipramine blocked UV\u2010induced MVP release in HaCaT keratinocytes, as well as XPA knockout mice. These studies support the concept that the photosensitivity associated with XPA involves PAF\u2010 and aSMase\u2010mediated MVP release and provides a potential pharmacologic target in treating this form of photosensitivity.<\/jats:p>","DOI":"10.1111\/php.13915","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T07:29:20Z","timestamp":1706599760000},"page":"1457-1466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evidence for the involvement of keratinocyte\u2010derived microvesicle particles in the photosensitivity associated with xeroderma pigmentosum type A deficiency"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6895-4765","authenticated-orcid":false,"given":"Lea","family":"Christian","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Wright State University  Dayton Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3426-8449","authenticated-orcid":false,"given":"Pranali","family":"Manjrekar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Wright State University  Dayton Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Henkels","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Wright State University  Dayton Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7114-7796","authenticated-orcid":false,"given":"Christine\u00a0M.","family":"Rapp","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Wright State University  Dayton Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risha","family":"Annamraju","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Wright State University  Dayton Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0350-9872","authenticated-orcid":false,"given":"Rushabh P.","family":"Lohade","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Wright State University  Dayton Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikshita","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Wright State University  Dayton Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8976-7969","authenticated-orcid":false,"given":"M. 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