Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells

Lohse, AW; Knolle, Percy A.; Bilo, K; Uhrig, A.; Waldmann, Christine; Ibe, Masaki; Schmitt, Edgar; Gerken, Guido; Büschenfelde, K-H Meyer zum

doi:10.1053/gast.1996.v110.pm8613007

Cited by 207 publications

(152 citation statements)

References 3 publications

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…In another set of experiments, recombinant murine interleukin-6 (50 ng/mL) was added. After 4 days, 3 H-thymidine was added to the culture, and after and additional 18 hours, 3 H thymidine uptake was assessed by ␤-scintillation counting. The suppressed proliferation of CD4 ϩ T cells (in the presence of Treg) minus proliferation of Treg alone (background) is given as percentage of the non-suppressed proliferation of CD4 ϩ T cells (in the absence of CD25 ϩ Treg):…”

Section: Methodsmentioning

confidence: 99%

“…1 Indeed, the most prevalent professional APC in liver, liver sinusoidal endothelial cells (LSEC) and Kupffer cells (KC), 2,3 have been shown to actively induce immune tolerance. 2,4,5 In addition, hepatocytes, which can upregulate expression of class II molecules of the major histocompatibility complex (MHC II) during hepatitis 6 and may then serve as APC for CD4 ϩ T lymphocytes, 7 also have been implicated in the induction of immune tolerance.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Murine Liver Antigen Presenting Cells Control Suppressor Activity of CD4+CD25+ Regulatory T Cells *

et al. 2005

View full text Add to dashboard Cite

U nder physiological conditions, the liver is basically free of inflammation and the resident antigen-presenting cells (APC) of the liver are believed to actively participate in the maintenance of hepatic immune tolerance. 1 Indeed, the most prevalent professional APC in liver, liver sinusoidal endothelial cells (LSEC) and Kupffer cells (KC), 2,3 have been shown to actively induce immune tolerance. 2,4,5 In addition, hepatocytes, which can upregulate expression of class II molecules of the major histocompatibility complex (MHC II) during hepatitis 6 and may then serve as APC for CD4 ϩ T lymphocytes, 7 also have been implicated in the induction of immune tolerance. 8 Nevertheless, rapid infiltration of the liver with inflammatory cells is induced during infection. However, the mechanisms that mediate the transition from hepatic immune tolerance to hepatic inflammation are not clear.CD4 ϩ CD25 ϩ regulatory T cells (Treg) are important mediators of peripheral immune tolerance: Treg can suppress the activation of autoreactive CD4 ϩ and CD8 ϩ T cells [9][10][11] and also control immune responses during infection. 12,13 Whether Treg are involved in the maintenance of hepatic immune tolerance is not clear; however, recent reports indicate that Treg indeed may suppress hepatic immunity to autoantigen 14 or virus. 15 Thus, it is likely that local suppressive Treg activity needs to be attenuated before liver inflammation can be induced.It has been reported recently that splenic dendritic cells have the capacity to regulate the suppressive activity of Treg 16 : normally, dendritic cells stimulate Treg-mediated suppression; however, in response to microbial stimuli, like lipopolysaccharide (LPS) or immune-stimulatory oli-

show abstract

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Murine Liver Antigen Presenting Cells Control Suppressor Activity of CD4+CD25+ Regulatory T Cells *

et al. 2005

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4] Liver sinusoidal endothelial cells (LSEC) exhibit unique properties, such as hyaluronic acid receptors 5,6 and production of coagulation factor VIII, 7 and play a role in the modulation of immune responses. [8][9][10] Angiogenesis requires proliferation of EC and mesenchymal cells as well as complex interactions between regulators of vasculogenesis and blood vessel maturation. 11 Recent insights helped focus interest in the potential of EC in cell and gene therapies, ranging from blood vessel repair to organ reconstitution.…”

Section: E Ndothelial Cells (Ec) Play Critical Roles In Orga-mentioning

confidence: 99%

Hepatic Targeting of Transplanted Liver Sinusoidal Endothelial Cells in Intact Mice *

et al. 2005

View full text Add to dashboard Cite

Targeting of cells to specific tissues is critical for cell therapy. To study endothelial cell targeting, we isolated mouse liver sinusoidal endothelial cells (LSEC) and examined cell biodistributions in animals. To identify transplanted LSEC in tissues, we labeled cells metabolically with DiIconjugated acetylated low density lipoprotein particles (DiI-Ac-LDL) or 111 Indium-oxine, used LSEC from Rosa26 donors expressing ␤-galactosidase or Tie-2-GFP donors with green fluorescent protein (GFP) expression, and tranduced LSEC with a GFP-lentiviral vector. LSEC efficiently incorporated 111 Indium and DiI-Ac-LDL and expressed GFP introduced by the lentiviral vector. Use of radiolabeled LSEC showed differences in cell biodistributions in relation to the cell transplantation route. After intraportal injection, LSEC were largely in the liver (60 ؎ 13%) and, after systemic intravenous injection, in lungs (67 ؎ 9%); however, after intrasplenic injection, only some LSEC remained in the spleen (29 ؎ 10%; P < .01), whereas most LSEC migrated to the liver or lungs. Transplanted LSEC were found in the liver, lungs, and spleen shortly after transplantation, whereas longer-term cell survival was observed only in the liver. Transplanted LSEC were distinct from Kupffer cells with expression of Tie-2 promoter-driven GFP and of CD31, without F4/80 reactivity. In further studies using radiolabeled LSEC, we established that the manipulation of receptor-mediated cell adhesion in liver sinusoids or the manipulation of blood flow-dependent cell exit from sinusoids improved intrahepatic retention of LSEC to 89 ؎ 7% and 89 ؎ 5%, respectively (P < .01). In conclusion, the targeting of LSEC to the liver and other organs is directed by vascular bed-specific mechanisms, including blood flow-related processes, and cell-specific factors. These findings may facilitate analysis of LSEC for cell and gene therapy applications. (HEPATOLOGY 2005;42:140-148.)

show abstract

“…Prostaglandin E 2 was identified to down-regulate IL-6 production in KC [13]. Furthermore, we have recently shown that SEC and KC induce antigen-specific T cell activation and are therefore involved in the local immune response [14]. Now we aimed to investigate the regulation of the inflammatory reaction in these cells in response to a non-specific proinflammatory stimulus (endotoxin/ lipopolysaccharide (LPS)).…”

Section: Introductionmentioning

confidence: 99%

Regulation of endotoxin-induced IL-6 production in liver sinusoidal endothelial cells and Kupffer cells by IL-10

Knolle¹,

Löser²,

Protzer³

et al. 1997

Clinical and Experimental Immunology

Self Cite

View full text Add to dashboard Cite

SUMMARYSinusoidal endothelial cells and Kupffer cells are the first cell populations in the liver that come into contact with gut-derived endotoxin in portal blood. Although endotoxin concentrations as high as 1 ng/ml are physiologically present in portal blood, no local inflammation is seen. We show that the proinflammatory cytokine IL-6, which is central to the development of inflammatory reactions in the liver, is produced by sinusoidal endothelial cells and Kupffer cells in response to low concentrations of endotoxin (100 pg/ml to 1 ng/ml). The anti-inflammatory cytokine IL-10 down-regulated endotoxin-induced IL-6 release in endothelial and Kupffer cells. Importantly, Kupffer cells secreted IL-10 after endotoxin stimulation and may therefore participate in the local regulation of inflammation. We have found that IL-6 secretion in Kupffer cells is tightly regulated by endogenous IL-10, because increased IL-6 secretion resulted when neutralizing antibodies to IL-10 were added to resting and endotoxin-challenged Kupffer cells. Furthermore, repeated exposure of endothelial cells to endotoxin induced a state of tolerance which resulted in decreased release of IL-6 in response to a second endotoxin challenge. Our results support the notion that inflammatory reactions in the liver in response to endotoxin are down-regulated by local release of the anti-inflammatory cytokine IL-10 that is produced by Kupffer cells.

show abstract

Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells

Cited by 207 publications

References 3 publications

Murine Liver Antigen Presenting Cells Control Suppressor Activity of CD4+CD25+ Regulatory T Cells *

Murine Liver Antigen Presenting Cells Control Suppressor Activity of CD4+CD25+ Regulatory T Cells *

Hepatic Targeting of Transplanted Liver Sinusoidal Endothelial Cells in Intact Mice *

Regulation of endotoxin-induced IL-6 production in liver sinusoidal endothelial cells and Kupffer cells by IL-10

Contact Info

Product

Resources

About