{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:33:37Z","timestamp":1783722817753,"version":"3.55.0"},"reference-count":63,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T00:00:00Z","timestamp":1595548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004348","name":"Stockholms L\u00e4ns Landsting","doi-asserted-by":"publisher","award":["20170127"],"award-info":[{"award-number":["20170127"]}],"id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Are carotid bodies (CBs) modulated by the damage\u2010associated molecular patterns (DAMPs) and humoral factors of aseptic tissue injury?<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What are the main findings and their importance?<\/jats:bold><\/jats:p>\n<jats:p>DAMPs (HMGB1, S100 A8\/A9) and blood plasma from rats subjected to tibia surgery, a model of aseptic injury, stimulate the release of neurotransmitters (ATP, dopamine) and TNF\u2010\u03b1 from <jats:italic>ex vivo<\/jats:italic> rat CBs. All\u2010thiol HMGB1 mediates upregulation of immune\u2010related biological pathways. These data suggest regulation of CB function by endogenous mediators of innate immunity.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The glomus cells of carotid bodies (CBs) are the primary sensors of arterial partial O<jats:sub>2<\/jats:sub> and CO<jats:sub>2<\/jats:sub> tensions and moreover serve as multimodal receptors responding also to other stimuli, such as pathogen\u2010associated molecular patterns (PAMPs) produced by acute infection. Modulation of CB function by excessive amounts of these immunomodulators is suggested to be associated with a detrimental hyperinflammatory state. We have hypothesized that yet another class of immunomodulators, endogenous danger\u2010associated molecular patterns (DAMPs), released upon aseptic tissue injury and recognized by the same pathogen recognition receptors as PAMPs, might modulate the CB activity in a fashion similar to PAMPs. We have tested this hypothesis by exposing rat CBs to various DAMPs, such as HMGB1 (all\u2010thiol and disulfide forms) and S100 A8\/A9 in a series of <jats:italic>ex vivo<\/jats:italic> experiments that demonstrated the release of dopamine and ATP, neurotransmitters known to mediate CB homeostatic responses. We observed a similar response after incubating CBs with conditioned blood plasma obtained from the rats subjected to tibia surgery, a model of aseptic injury. In addition, we have investigated global gene expression in the rat CB using an RNA sequencing approach. Differential gene expression analysis showed all\u2010thiol HMGB1\u2010driven upregulation of a number of prominent pro\u2010inflammatory markers including <jats:italic>Il1\u03b1<\/jats:italic> and <jats:italic>Il1\u03b2<\/jats:italic>. Interestingly, conditioned plasma had a more profound effect on the CB transcriptome resulting in inhibition rather than activation of the immune\u2010related pathways. These data are the first to suggest potential modulation of CB function by endogenous mediators of innate immunity.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep088705","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T19:41:52Z","timestamp":1594496512000},"page":"1634-1647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The impact of damage\u2010associated molecular patterns on the neurotransmitter release and gene expression in the <i>ex vivo<\/i> rat carotid body"],"prefix":"10.1113","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9801-2736","authenticated-orcid":false,"given":"Souren","family":"Mkrtchian","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Section for Anesthesiology and Intensive Care Medicine Karolinska Institutet  Stockholm 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