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dc.contributor.authorBhandari, Sabin
dc.contributor.authorLi, Ruomei
dc.contributor.authorSimon-Santamaria, Jaione
dc.contributor.authorMcCourt, Peter Anthony
dc.contributor.authorJohansen, Steinar Daae
dc.contributor.authorSmedsrød, Bård
dc.contributor.authorMartinez, Inigo Zubiavrre
dc.contributor.authorSørensen, Karen Kristine
dc.date.accessioned2020-12-01T14:35:36Z
dc.date.available2020-12-01T14:35:36Z
dc.date.issued2020-11-27
dc.description.abstract<i>Background</i> - Liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs; liver resident macrophages) form the body’s most effective scavenger cell system for the removal of harmful blood-borne substances, ranging from modified self-proteins to pathogens and xenobiotics. Controversies in the literature regarding the LSEC phenotype pose a challenge when determining distinct functionalities of KCs and LSECs. This may be due to overlapping functions of the two cells, insufficient purification and/or identification of the cells, rapid dedifferentiation of LSECs in vitro, or species differences. We therefore characterized and quantitatively compared expressed gene products of freshly isolated, highly pure LSECs (fenestrated SE-1/FcγRIIb2<sup>+</sup>) and KCs (CD11b/c<sup>+</sup>) from Sprague Dawley, Crl:CD (SD), male rats using high throughput mRNA-sequencing and label-free proteomics.<p> <p><i>Results</i> - We observed a robust correlation between the proteomes and transcriptomes of the two cell types. Integrative analysis of the global molecular profile demonstrated the immunological aspects of LSECs. The constitutive expression of several immune genes and corresponding proteins of LSECs bore some resemblance with the expression in macrophages. LSECs and KCs both expressed high levels of scavenger receptors (SR) and C-type lectins. Equivalent expression of SR-A1 (Msr1), mannose receptor (Mrc1), SR-B1 (Scarb1), and SR-B3 (Scarb2) suggested functional similarity between the two cell types, while functional distinction between the cells was evidenced by LSEC-specific expression of the SRs stabilin-1 (Stab1) and stabilin-2 (Stab2), and the C-type lectins LSECtin (Clec4g) and DC-SIGNR (Clec4m). Many immune regulatory factors were differentially expressed in LSECs and KCs, with one cell predominantly expressing a specific cytokine/chemokine and the other cell the cognate receptor, illustrating the complex cytokine milieu of the sinusoids. Both cells expressed genes and proteins involved in antigen processing and presentation, and lymphocyte co-stimulation.<p> <p><i>Conclusions</i> - Our findings support complementary and partly overlapping scavenging and immune functions of LSECs and KCs. This highlights the importance of including LSECs in studies of liver immunity, and liver clearance and toxicity of large molecule drugs and nano-formulations.en_US
dc.identifier.citationBhandari S, Li R, Simon-Santamaria J, McCourt PAG, Johansen S.D., Smedsrød b, Martinez IZ, Sørensen KK. Transcriptome and proteome profiling reveal complementary scavenger and immune features of rat liver sinusoidal endothelial cells and liver macrophages. BMC Molecular and Cell Biology. 2020;21en_US
dc.identifier.cristinIDFRIDAID 1854255
dc.identifier.doihttps://doi.org/10.1186/s12860-020-00331-9
dc.identifier.issn2661-8850
dc.identifier.urihttps://hdl.handle.net/10037/19952
dc.language.isoengen_US
dc.publisherBMCen_US
dc.relation.ispartofBhandari, S. (2021). Molecular profiling of the liver sinusoidal endothelial cell – a multi-omics approach. (Doctoral thesis). <a href=https://hdl.handle.net/10037/21896>https://hdl.handle.net/10037/21896</a>.
dc.relation.journalBMC Molecular and Cell Biology
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleTranscriptome and proteome profiling reveal complementary scavenger and immune features of rat liver sinusoidal endothelial cells and liver macrophagesen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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