Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1)

Øie, Cristina Ionica; Appa, Rupa Shree; Hilden, Ida; Petersen, H; Gruhler, Albrecht; Smedsrød, Bård; Hansen, John‐Bjarne

doi:10.1016/j.jhep.2011.03.013

Cited by 25 publications

(15 citation statements)

References 44 publications

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“…Since we showed that the rMASP-1/C1-Inhibitor complex did not disintegrate within 24 hours, an alternative mechanism should be presumed. As the C1-Inhibitor complex – but not the active C1-Inhibitor – binds to low-density lipoprotein receptor-related proteins (LRPs) [40] expressed on endothelial cells [41], it appears plausible that the rMASP-1/C1-Inhibitor complex may induce IL-8 production via LRPs after 24 hours of activation.…”

Section: Discussionmentioning

confidence: 99%

MASP-1 Induces a Unique Cytokine Pattern in Endothelial Cells: A Novel Link between Complement System and Neutrophil Granulocytes

et al. 2014

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Microbial infection urges prompt intervention by the immune system. The complement cascade and neutrophil granulocytes are the predominant contributors to this immediate anti-microbial action. We have previously shown that mannan-binding lectin-associated serine protease-1 (MASP-1), the most abundant enzyme of the complement lectin pathway, can induce p38-MAPK activation, NFkappaB signaling, and Ca2+-mobilization in endothelial cells. Since neutrophil chemotaxis and transmigration depends on endothelial cell activation, we aimed to explore whether recombinant MASP-1 (rMASP-1) is able to induce cytokine production and subsequent neutrophil chemotaxis in human umbilical vein endothelial cells (HUVEC). We found that HUVECs activated by rMASP-1 secreted IL-6 and IL-8, but not IL-1alpha, IL-1ra, TNFalpha and MCP-1. rMASP-1 induced dose-dependent IL-6 and IL-8 production with different kinetics. rMASP-1 triggered IL-6 and IL-8 production was regulated predominantly by the p38-MAPK pathway. Moreover, the supernatant of rMASP-1-stimulated HUVECs activated the chemotaxis of neutrophil granulocytes as an integrated effect of cytokine production. Our results implicate that besides initializing the complement lectin pathway, MASP-1 may activate neutrophils indirectly, via the endothelial cells, which link these effective antimicrobial host defense mechanisms.

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Section: Discussionmentioning

confidence: 99%

MASP-1 Induces a Unique Cytokine Pattern in Endothelial Cells: A Novel Link between Complement System and Neutrophil Granulocytes

et al. 2014

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“…The isolation protocol used for the liver sinusoidal endothelial cells (LSEC) was adapted from previously described methods (17). Briefly, after perfusion with dissociation buffer, the liver was digested with collagenase I (0.025%) and collagenase II (0.025%) (Sigma-Aldrich) in digestion buffer supplemented with 50 g/ml trypsin inhibitor (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

“…To study the role of individual liver cell types in limiting NS2 H126R replication, we purified each of the three major cell types, representing Ͼ95% of liver cells, and cultured them in vitro. Specifically, we focused on the parenchymal cells (the hepatocytes) and the nonparenchymal Kupffer cells (KC) and liver sinusoidal endothelial cells (LSEC), using established isolation and culture methods, as described elsewhere (16,17). To assess the purity of the liver cell preparations, we used the nonspecific stain DAPI in all the tests to identify the nuclei.…”

Section: Isolation and Purification Of Kupffer Cells (Kc) Liver Sinumentioning

confidence: 99%

Antagonism of RNase L Is Required for Murine Coronavirus Replication in Kupffer Cells and Liver Sinusoidal Endothelial Cells but Not in Hepatocytes

Weiss

2016

J Virol

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Mouse hepatitis virus strain A59 infection of mice is a useful tool for studying virus-host interaction during hepatitis development. The NS2H126R mutant is attenuated in liver replication due to loss of phosphodiesterase activity, which the wild-type (WT) virus uses to block the 2=,5=-oligoadenylate synthetase (OAS)-RNase L (RNase L) antiviral pathway. IMPORTANCE Mouse hepatitis virus infection of mice provides a useful tool for studying virus-host interactions during hepatitis development. The NS2H126R mutant is attenuated in liver replication due to loss of phosphodiesterase activity, by which the wild-type virus blocks the potent OAS-RNase L antiviral pathway. RNase L activation by NS2 H126R is cell type dependent and correlates with high basal expression levels of OAS, as found in myeloid cells. We showed that the hepatocytes that comprise the liver parenchyma do not activate RNase L when infected with NS2 H126R or restrict replication. However, both Kupffer cells (KC) (i.e., the liver-resident macrophages) and the liver sinusoidal endothelial cells (LSEC) which line the sinusoids activate RNase L in response to NS2 H126R . These data suggest that KC and LSEC prevent viral spread into the parenchyma, preventing hepatitis. Furthermore, hepatocytes express undetectable levels of OASs and RNase L, which likely explains the lack of RNase L activation during NS2 H126R infection. M ouse hepatitis virus (MHV) belongs to the order Nidovirales,family Coronaviridae, and genus Betacoronavirus. Coronaviruses are enveloped, nonsegmented positive-strand RNA viruses (1). MHV strain A59 induces moderate to severe hepatitis in infection of mice (2); replication and the consequent liver pathogenesis are dependent on the 2=,5=-phosphodiesterase (PDE) activity of the viral accessary protein NS2 (3).The 2=,5=-oligoadenylate (2-5A) synthetase (OAS)-RNase L pathway is involved in potent interferon (IFN)-induced antiviral activity (4). Upon infection by diverse viruses, including the human-liver-pathogenic hepatitis C virus (5, 6), double-stranded RNA (dsRNA) is detected by OAS proteins. Four mouse OAS species (OAS1a/g, OAS2, OAS3, and OASL2) and 3 human OAS species (OAS1, OAS2, and OAS3) can bind dsRNA in vitro and be activated to generate 2-5A (7), the latter binding to and promoting activation and dimerization of RNase L, which results in both cellular and viral RNA degradation and thus in inhibition of viral replication (7,8).The PDE (NS2) of MHV cleaves 2-5A and inhibits the activation of RNase L (3). An A59 mutant, NS2H126R , which encodes a catalytically inactive PDE, replicates to a minimal extent in the mouse liver and causes minor to no liver damage during infection (3). Previous studies have illuminated that the activation of the OAS-RNase L antiviral pathway is cell type dependent. Bone marrow-derived macrophages (BMM) and bone marrow-derived dendritic cells (BMDC) as well as microglia, brain-resident macrophages, limit NS2 H126R replication by activating the OAS-RNase L pathway. The basal mRNA expression lev...

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“…Confluent cells formed a polygonal flat “cobblestone” monolayer - characteristic of cultured ECs (Figure 1B). Furthermore LSEC-uniLTs expressed the endothelial cell surface markers CD105 and CD146 (Additional file 1: Figure S1D) and could take up high amounts of low-density lipoproteins (Additional file 1: Figure S1E), a function typical of LSEC, but not other endothelial cells [25]. …”

Section: Resultsmentioning

confidence: 99%

A new reporter mouse cytomegalovirus reveals maintained immediate-early gene expression but poor virus replication in cycling liver sinusoidal endothelial cells

Dağ

Weingärtner

Butueva

et al. 2013

Virol J

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BackgroundThe MCMV major immediate early promoter/enhancer (MIEP) is a bidirectional promoter that drives the expression of the three immediate early viral genes, namely ie1, ie2 and ie3. The regulation of their expression is intensively studied, but still incompletely understood.MethodsWe constructed a reporter MCMV, (MCMV-MIEPr) expressing YFP and tdTomato under the control of the MIEP as proxies of ie1 and ie2, respectively. Moreover, we generated a liver sinusoidal endothelial cell line (LSEC-uniLT) where cycling is dependent on doxycycline. We used these novel tools to study the kinetics of MIEP-driven gene expression in the context of infection and at the single cell level by flow cytometry and by live imaging of proliferating and G0-arrested cells.ResultsMCMV replicated to higher titers in G0-arrested LSEC, and cycling cells showed less cytopathic effect or YFP and tdTomato expression at 5 days post infection. In the first 24 h post infection, however, there was no difference in MIEP activity in cycling or G0-arrested cells, although we could observe different profiles of MIEP gene expression in different cell types, like LSECs, fibroblasts or macrophages. We monitored infected LSEC-uniLT in G0 by time lapse microscopy over five days and noticed that most cells survived infection for at least 96 h, arguing that quick lysis of infected cells could not account for the spread of the virus. Interestingly, we noticed a strong correlation between the ratio of median YFP and tdTomato expression and length of survival of infected cells.ConclusionBy means of our newly developed genetic tools, we showed that the expression pattern of MCMV IE1 and IE2 genes differs between macrophages, endothelial cells and fibroblasts. Substantial and cell-cycle independent differences in the ie1 and ie2 transcription could also be observed within individual cells of the same population, and marked ie2 gene expression was associated with longer survival of the infected cells.

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Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1)

Abstract: Background and Aims:The low density lipoprotein receptor-related protein-1 (LRP-1)

Cited by 25 publications

References 44 publications

MASP-1 Induces a Unique Cytokine Pattern in Endothelial Cells: A Novel Link between Complement System and Neutrophil Granulocytes

MASP-1 Induces a Unique Cytokine Pattern in Endothelial Cells: A Novel Link between Complement System and Neutrophil Granulocytes

Antagonism of RNase L Is Required for Murine Coronavirus Replication in Kupffer Cells and Liver Sinusoidal Endothelial Cells but Not in Hepatocytes

A new reporter mouse cytomegalovirus reveals maintained immediate-early gene expression but poor virus replication in cycling liver sinusoidal endothelial cells

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