ライフサイエンスコーパス: LSEC

1 LSEC demonstrated a high capacity for Ag uptake in vitro

2 LSEC efficiently incorporated (111)Indium and DiI-Ac-LDL

3 LSEC label-retaining cells and progenitors were identifi

4 LSEC secrete factors that promote HCV infection and tran

5 LSEC-restricted deletion of Gata4 caused transformation

6 LSECs and hepatocytes contained comparable numbers of fV

7 LSECs are highly fenestrated cells; they contain transce

8 LSECs are involved in induction of immune tolerance, but

9 LSECs block adaptive immunogenic responses to Ag and ind

10 LSECs expressed functional retinal dehydrogenases and co

11 LSECs secreted active fVIII into the culture medium.

12 In addition, LSECs gain enhanced capacity to capture Ag and induce T

13 Additionally, LSECs potentially are targets for a fVIII transgene duri

14 methylnitrosamine; within 5 days, 40% of all LSECs came from engrafted BM SPCs.

15 ortions, hepatocytes (parenchymal cells) and LSEC (non-parenchymal cells).

16 prevented by RNase L activity in both KC and LSEC but not in hepatocytes.

17 were observed for the two viruses in KC and LSEC from RNase L(-/-) mice, demonstrating that both use

18 to NS2(H126R) These data suggest that KC and LSEC prevent viral spread into the parenchyma, preventin

19 and progenitors were identified in liver and LSEC progenitors in BM.

20 The numbers of Kupffer cells and LSECs, the level of clotting factor X, and hepatocyte in

21 udies of subcellular ultrastructures such as LSEC fenestrations.

22 rmation of fenestration after engraftment as LSECs, and exacerbated dimethylnitrosamine injury.

23 thylnitrosamine, repopulated the sinusoid as LSECs and reduced liver injury.

24 BM LSEC progenitors did not contribute to normal LSEC turno

25 quarter of the LSECs were BM derived, and BM LSEC progenitors differentiated into fenestrated LSECs.

26 the relative contribution of resident and BM LSEC progenitors.

27 blish in rats whether liver injury causes BM LSEC progenitor cells to engraft in the liver and provid

28 However, after partial hepatectomy, BM LSEC progenitor proliferation and mobilization to the ci

29 esent in liver and BM, and recruitment of BM LSEC progenitors is necessary for normal liver regenerat

30 in recovery from partial hepatectomy than BM LSEC progenitors, but, when infused after injury, these

31 Further analysis revealed that BM LSEC progenitors expressed substantially more HGF and we

32 CC chemokine receptor 9 (CCR9) expression by LSEC-primed CD4(+) T cells.

33 , lack of liver sinusoidal endothelial cell (LSEC) fenestration, and formation of an organized baseme

34 ed mouse liver sinusoidal endothelial cells (LSEC) and examined cell biodistributions in animals.

35 ted with liver sinusoidal endothelial cells (LSEC) and only approximately 25% with KC.

36 essed on liver sinusoidal endothelial cells (LSEC) and that the liver is the major site of small immu

37 ved that liver sinusoidal endothelial cells (LSEC) derived from ethanol-fed rats showed several fold

38 Liver sinusoidal endothelial cells (LSEC) have been reported to express MHC class II, CD80,

39 tes with liver sinusoidal endothelial cells (LSEC) significantly increases the ability of hepatocytes

40 cells by liver sinusoidal endothelial cells (LSEC) supported migration into gut and gut-associated ly

41 and the liver sinusoidal endothelial cells (LSEC) which line the sinusoids activate RNase L in respo

42 g hepatocytes, sinusoidal endothelial cells (LSEC), Kupffer cells, and biliary epithelial cells.

43 fied the liver sinusoidal endothelial cells (LSEC), marked by FcgammaRIIb, as the cell within the liv

44 ngly, in liver sinusoidal endothelial cells (LSEC), the cells that form a barrier between blood and l

45 Liver sinusoidal endothelial cells (LSECs) act as a filter between blood and the hepatocytes

46 such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), are the first

47 f murine liver sinusoidal endothelial cells (LSECs) and hepatocytes, but not Kupffer cells.

48 hich rat liver sinusoidal endothelial cells (LSECs) are repopulated in the reperfused transplanted li

49 (HGF) in liver sinusoidal endothelial cells (LSECs) are thought to drive liver regeneration.

50 Liver sinusoidal endothelial cells (LSECs) are unique organ-resident APCs capable of Ag cros

51 Liver sinusoidal endothelial cells (LSECs) are uniquely differentiated to fulfill important

52 ets with liver sinusoidal endothelial cells (LSECs) by immunohistochemistry.

53 ate that liver sinusoidal endothelial cells (LSECs) constitute a unique population of phenotypically

54 Liver sinusoidal endothelial cells (LSECs) defenestrate and capillarize in response to aging

55 Liver sinusoidal endothelial cells (LSECs) differ, both structurally and functionally, from

56 Liver sinusoidal endothelial cells (LSECs) have long been noted to contribute to liver regen

57 re the role of sinusoidal endothelial cells (LSECs) in the adult liver, we studied the effects of vas

58 Liver sinusoidal endothelial cells (LSECs) make up a large proportion of the nonparenchymal

59 r cells, liver sinusoidal endothelial cells (LSECs), hepatocytes, scavenger receptors, clotting facto

60 ation of liver sinusoidal endothelial cells (LSECs), precedes the onset of hepatic fibrosis.

61 usoid as liver sinusoidal endothelial cells (LSECs).

62 aling in liver sinusoidal endothelial cells (LSECs).

63 ance are liver sinusoidal endothelial cells (LSECs).

64 GGTA1, CMAH LSECs exhibited reduced levels of human platelet binding

65 VIII activity and AcLOL uptake in cocultured LSECs through the production of short-range paracrine si

66 In conclusion, LSEC progenitor cells are present in liver and BM, and r

67 Under certain conditions, LSECs can switch from a tolerogenic to an immunogenic st

68 , in the absence of exogenous costimulation, LSEC induced negligible proliferation of CD4(+) or CD8(+

69 However, unlike DC, LSEC had low or absent expression of MHC class II, CD86,

70 unctional engraftment of bone marrow-derived LSECs after cold ischemia and warm reperfusion.

71 are necessary to maintain the differentiated LSEC phenotype.

72 The switch from discontinuous LSECs to continuous ECs during embryogenesis caused live

73 pecifically transduced liver sinusoidal ECs (LSECs) but not Kupffer cells, which were mainly transduc

74 continuous cell layer, liver sinusoidal ECs (LSECs) constitute discontinuous, permeable microvessels.

75 Herein, we report that liver sinusoidal ECs (LSECs; defined as CD146(+)CD45(-)) exhibit increased int

76 For example, in contrast to other ECs, LSECs possess fenestrations, have low detectable levels

77 , NPCs-Kupffer (KC), sinusoidal endothelial (LSEC) and stellate cells (SC) are major cellular compone

78 By using magnetically enriched LSEC (CD146(+)) populations, we show evidence of marked

79 progenitors differentiated into fenestrated LSECs.

80 n of T regulatory cells, in hepatic fibrosis LSECs induce an immunogenic T cell phenotype capable of

81 unlike LSECs in normal livers, in fibrosis, LSECs do not veto dendritic cell priming of T cells.

82 These studies identify a role for LSEC and BMP4 in HCV infection and highlight BMP4 as a n

83 m the enriched nonparenchymal cell fraction, LSEC (CD45(-)) were then isolated to 99% purity using im

84 as an organ-specific angiokine derived from LSECs.

85 f bone marrow-derived cells into functioning LSECs is routinely between 1% and 5%.

86 ter fibrotic liver injury from hepatotoxins, LSECs become highly proinflammatory and secrete an array

87 on of inductive VEGFR2(+)Id1(+)Wnt2(+)HGF(+) LSECs with hepatocytes provides an effective strategy to

88 ced with Wnt2 and HGF (Id1(-/-)Wnt2(+)HGF(+) LSECs) re-establishes an inductive vascular niche in the

89 or (huCD105-LV) transduced exclusively human LSECs in mice transplanted with human liver ECs.

90 Primary human LSECs (HLSECs) and immortalized liver endothelial cells

91 enic transplantation of Id1(+/+) or Id1(-/-) LSECs transduced with Wnt2 and HGF (Id1(-/-)Wnt2(+)HGF(+

92 over, most (90%) liver RIIb was expressed in LSEC, the remainder in Kupffer cells.

93 al time PCR we found messenger expression in LSEC to be about 5 times higher than in hepatocytes.

94 An absent FcRgamma in LSEC implied that RIIb is the sole FcgammaR expressed.

95 on and elucidated the mechanisms involved in LSEC-induced T cell immunity.

96 vitro co-cultures, VEGFR2-Id1 activation in LSECs stimulates hepatocyte proliferation.

97 EGFR2-Id1-mediated inductive angiogenesis in LSECs through release of angiocrine factors Wnt2 and HGF

98 the liver, we conditionally deleted Bmp2 in LSECs using EC subtype-specific Stab2-Cre mice.

99 Disruption of Notch1 signaling in LSECs leads to spontaneous formation of angiosarcoma, in

100 After intraportal injection, LSEC were largely in the liver (60 +/- 13%) and, after s

101 merging data suggest that even after injury, LSEC expression of HGF does not increase greatly.

102 Furthermore, whereas in normal livers, LSECs are active in the generation of T regulatory cells

103 rast to endothelial progenitor cells, mature LSECs express little HGF.

104 n recruited to the liver, rather than mature LSECs, drive liver regeneration.

105 a critical role for death receptor-mediated LSEC injury and show the first evidence that Kupffer cel

106 e spleen (29 +/- 10%; P < .01), whereas most LSEC migrated to the liver or lungs.

107 e transcription factor GATA4 controls murine LSEC specification and function.

108 compare the phenotype and function of murine LSEC and DC.

109 SEC progenitors did not contribute to normal LSEC turnover in the liver.

110 n of BMP4 abrogated the proviral activity of LSEC-conditioned media.

111 Flow cytometric analysis of LSEC demonstrated high expression of CD31, von Willebran

112 These findings may facilitate analysis of LSEC for cell and gene therapy applications.

113 eneration, owing to diminished expression of LSEC-derived angiocrine factors, including hepatocyte gr

114 been purported to be a specific function of LSEC, we found DC captured acetylated low-density lipopr

115 ion of both SE-1 and phenotypic functions of LSEC such as factor VIII activity and AcLOL uptake in co

116 egeneration was compromised, but infusion of LSEC progenitors rescued the defect.

117 Maintenance of LSEC differentiation requires vascular endothelial growt

118 cell deficiency did not reverse the onset of LSEC apoptosis/damage.

119 tion of KC by gadolinium(III) chloride or of LSEC by cyclophosphamide partially restores liver replic

120 results lead us to propose a new paradigm of LSEC and HDL in clearing LPS with a potential to avoid i

121 Notably, the ratio of LSEC-KC-associated LPS remained unchanged 45 min after i

122 Restoration of LSEC differentiation in vivo promotes HSC quiescence, en

123 We investigated whether restoration of LSEC differentiation would normalize crosstalk with acti

124 sinusoids improved intrahepatic retention of LSEC to 89 +/- 7% and 89 +/- 5%, respectively (P < .01).

125 lated that, in liver fibrosis, a reversal of LSEC function from tolerogenic to proinflammatory and im

126 Thus, we proposed that RIIb of LSEC eliminates blood-borne SIC, thereby controlling imm

127 The state of LSEC differentiation plays a pivotal role in HSC activat

128 In conclusion, the targeting of LSEC to the liver and other organs is directed by vascul

129 C-associated transcripts and upregulation of LSEC-associated genes.

130 In contrast, bone marrow progenitor cells of LSECs (BM SPCs), which are rich in HGF, are recruited to

131 Primary cultures of LSECs were established in which fVIII mRNA levels were i

132 ylnitrosamine caused extensive denudation of LSECs at 24 hours, followed by centrilobular hemorrhagic

133 Moreover, depletion of LSECs from fibrotic liver cultures mitigates the proinfl

134 maintains quiescence and differentiation of LSECs in adult mice.

135 capillarization (restored differentiation of LSECs) without directly affecting activation of HSCs or

136 for intestinal DCs but is also a feature of LSECs.

137 We found that the majority of LSECs in livers cold-stored for 18 hours in University o

138 nvestigated whether functional maturation of LSECs can be achieved by TLR ligand stimulation and eluc

139 ver, little is known about the mechanisms of LSECs to induce T cell immunity.

140 We demonstrate that pretreatment of LSECs with palmitoyl-3-cysteine-serine-lysine-4 (P3C; TL

141 th a persistent increase in proliferation of LSECs.

142 ffer a critical understanding of the role of LSECs in modulating intrahepatic immunity and inflammati

143 ulation and that the immunological status of LSECs was dependent upon the balance between programmed

144 ffer cells are essential to the viability of LSECs, which appears to be mediated through glycoprotein

145 ion of alpha(4) beta(7) integrin and CCR9 on LSEC-primed CD4(+) T cells, consequently reducing their

146 V/fibronectin as having a positive effect on LSEC survival.

147 RIIb on LSEC, a major scavenger, keeps SIC blood concentrations

148 We found that S1P(1) was enriched on LSECs in vivo and in primary cell culture and that VPC23

149 a decrease in glycoprotein 130 expression on LSECs, suggesting that STAT3 activation may protect thes

150 duce programmed death ligand 1 expression on LSECs, thereby favoring T cell proliferation and activat

151 to cross-contamination in the hepatocyte or LSEC preparations.

152 mulation of both angiogenesis and pathogenic LSEC capillarization, as well as demonstrating a role fo

153 Consistent with their phenotype, LSEC were poor stimulators of allogeneic T cells.

154 aused functional maturation of Ag-presenting LSECs and enabled them to activate virus-specific CD8(+)

155 hought to increase markedly in proliferating LSECs.

156 levels were indistinguishable from purified LSECs.

157 Use of radiolabeled LSEC showed differences in cell biodistributions in rela

158 In further studies using radiolabeled LSEC, we established that the manipulation of receptor-m

159 ory cytochemokines compared with control rat LSEC.

160 ally, ethanol-induced ET-1 expression in rat LSEC is regulated by miR-199, while in human endothelial

161 Rat LSECs were cultured with inhibitors and/or agonists and

162 ge vessel endothelial cells and repopulating LSECs.

163 Resident LSEC progenitors within their niche may play a smaller r

164 GF and were more proliferative than resident LSEC progenitors after partial hepatectomy.

165 of this pathway downstream from NO restores LSEC differentiation in vivo.

166 ver, after intrasplenic injection, only some LSEC remained in the spleen (29 +/- 10%; P < .01), where

167 We applied 3D-SIM to multi-color stained LSECs to acquire highly resolved overviews of large samp

168 -phosphate-stimulated and arsenic-stimulated LSEC oxidant generation and defenestration.

169 on of SR-B1 by flow cytometry, we found that LSEC expressed considerable amounts of SR-B1 while in he

170 to previous reports, our data indicate that LSEC alone are insufficient to activate naive T cells.

171 anged 45 min after infusion, indicating that LSEC independently processes the LPS.

172 We find that LSECs induce the hepatic expression of the LDL receptor

173 Our data suggest that LSECs undergo maturation exclusively in response to TLR1

174 The LSEC-mediated CD8(+) T cell immunity was initiated by so

175 A for factor IX, a hepatocyte marker, in the LSEC preparation, nor was there detectable mRNA for von

176 Thus, dysregulation of the LSEC phenotype is a critical step in the fibrotic proces

177 th factor (HGF) was identified as one of the LSEC-derived paracrine mediators promoting hepatocyte gr

178 ellular matrix and neighboring cells, on the LSEC phenotype in vitro.

179 h factor (VEGF)-A receptor-2 (VEGFR2) in the LSECs impairs the initial burst of hepatocyte proliferat

180 In the liver, one-quarter of the LSECs were BM derived, and BM LSEC progenitors different

181 Restoration of differentiation to LSECs led to quiescence of HSCs and regression of fibros

182 ential to induce gut homing is restricted to LSECs.

183 cent protein (GFP) expression, and tranduced LSEC with a GFP-lentiviral vector.

184 Transplanted LSEC were distinct from Kupffer cells with expression of

185 Transplanted LSEC were found in the liver, lungs, and spleen shortly

186 To identify transplanted LSEC in tissues, we labeled cells metabolically with DiI

187 ed the same results in acute ethanol-treated LSEC from control rats and human dermal microvascular en

188 ulate growth of hepatocytes in vitro, unless LSECs were also present in the culture.

189 Similarly, unlike LSECs in normal livers, in fibrosis, LSECs do not veto d

190 cles (DiI-Ac-LDL) or (111)Indium-oxine, used LSEC from Rosa26 donors expressing beta-galactosidase or

191 apoptosis, with a twofold decline in viable LSECs in CLP animals compared with sham controls.

192 ently tagged LPS-HDL complex associates with LSEC, suggesting that HDL facilitates LPS clearance.

193 oprotein (HDL)-mediated LPS association with LSEC early in the process.

194 We suggest that coculture with LSECs induces the emergence of a sinusoidal surface in p

195 e particles, the hepatocytes cocultured with LSECs showed a high level of HCV-like particle uptake.

196 t incorporating primary rat hepatocytes with LSECs, SCs, and KCs.

197 ing in vitro when compared with GGTA1 and WT LSECs.