Evaluation of components of the extracellular purinergic signaling system in human sepsis

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dc.authorid0000-0003-3616-1204
dc.contributor.authorLovászi, Marianna
dc.contributor.authorNémeth, Zoltán H.
dc.contributor.authorKeleştemur, Taha
dc.contributor.authorSánchez, Itzel V.
dc.contributor.authorAntonioli, Luca
dc.contributor.authorPacher, Pál
dc.contributor.authorWagener, Gebhard
dc.contributor.authorHaskó, György
dc.date.accessioned2024-06-11T05:15:01Z
dc.date.available2024-06-11T05:15:01Z
dc.date.issued2024
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.description.abstractObjective: Extracellular purines such as adenosine triphosphate (ATP), uridine triphosphate (UTP), and uridine diphosphate (UDP) and the ATP degradation product adenosine are biologically active signaling molecules, which accumulate at sites of metabolic stress in sepsis. They have potent immunomodulatory effects by binding to and activating P1 or adenosine and P2 receptors on the surface of leukocytes. Here we assessed the levels of extracellular purines, their receptors, metabolic enzymes, and cellular transporters in leukocytes of septic patients. Methods: Peripheral blood mononuclear cells (PBMCs), neutrophils, and plasma were isolated from blood obtained from septic patients and healthy control subjects. Ribonucleic acid was isolated from cells, and mRNA levels for purinergic receptors, enzymes, and transporters were measured. Adenosine triphosphate, UTP, UDP, and adenosine levels were evaluated in plasma. Results: Adenosine triphosphate levels were lower in septic patients than in healthy individuals, and levels of the other purines were comparable between the two groups. Levels of P1 and P2 receptors did not differ between the two patient groups. mRNA levels of ectonucleoside triphosphate diphosphohydrolase (NTPDase) 1 or CD39 increased, whereas those of NTPDase2, 3, and 8 decreased in PBMCs of septic patients when compared with healthy controls. CD73 mRNA was lower in PBMCs of septic than in healthy individuals. Equilibrative nucleoside transporter (ENT) 1 mRNA concentrations were higher and ENT2, 3, and 4 mRNA concentrations were lower in PBMCs of septic subjects when compared with healthy subjects. Concentrative nucleoside transporter (CNT) 1 mRNA levels were higher in PBMCs of septic versus healthy subjects, whereas the mRNA levels of CNT2, 3, and 4 did not differ. We failed to detect differences in mRNA levels of purinergic receptors, enzymes, and transporters in neutrophils of septic versus healthy subjects. Conclusion: Because CD39 degrades ATP to adenosine monophosphate (AMP), the lower ATP levels in septic individuals may be the result of increased CD39 expression. This increased degradation of ATP did not lead to increased adenosine levels, which may be explained by the decreased expression of CD73, which converts AMP to adenosine. Altogether, our results demonstrate differential regulation of components of the purinergic system in PBMCs during human sepsis.
dc.description.sponsorshipUnited States Department of Health & Human Servicesen_US
dc.description.sponsorshipNational Institutes of Health (NIH) - USAen_US
dc.identifier.citationLovászi, M., Németh, Z. H., Keleştemur, T., Sánchez, I. V., Antonioli, L., Pacher, P. ... Haskó, G. (2024). Evaluation of components of the extracellular purinergic signaling system in human sepsis. Shock, 61(4), 527-540. http://dx.doi.org/10.1097/SHK.0000000000002230
dc.identifier.doi10.1097/SHK.0000000000002230
dc.identifier.endpage540
dc.identifier.issn1073-2322
dc.identifier.issn1540-0514
dc.identifier.issue4
dc.identifier.pmid37752081
dc.identifier.scopus2-s2.0-85190408205
dc.identifier.scopusqualityQ1
dc.identifier.startpage527
dc.identifier.urihttp://dx.doi.org/10.1097/SHK.0000000000002230
dc.identifier.urihttps://hdl.handle.net/20.500.12511/12609
dc.identifier.volume61
dc.identifier.wos001200681000012en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorKeleştemur, Taha
dc.language.isoen
dc.relation.ecinfo:eu-repo/grantAgreement/R01HL158519-GH
dc.relation.ecinfo:eu-repo/grantAgreement/R01GM066189-GH
dc.relation.ecinfo:eu-repo/grantAgreement/R01DK113790-GH
dc.relation.ispartofShocken_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectImmunosuppression
dc.subjectInflammation
dc.subjectInjury
dc.subjectTrauma
dc.titleEvaluation of components of the extracellular purinergic signaling system in human sepsis
dc.typeArticle

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