scholarly journals Stabilins are expressed in bone marrow sinusoidal endothelial cells and mediate scavenging and cell adhesive functions

2009 ◽  
Vol 390 (3) ◽  
pp. 883-886 ◽  
Author(s):  
Hong Qian ◽  
Sophie Johansson ◽  
Peter McCourt ◽  
Bård Smedsrød ◽  
Marja Ekblom ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Cell Adhesive

Bone Marrow Sinusoidal Endothelium Undergoes DNA Damage and Repair Following Lethal Irradiation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4866-4866
Author(s):  
Xiao-Miao Li ◽  
Zhongbo Hu ◽  
Marda L. Jorgenson ◽  
John R. Wingard ◽  
William B. Slayton
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Endothelial Cells ◽  
Bone Marrow Transplant ◽  
Caspase 3 ◽  
Marrow Transplant ◽  
Sinusoidal Endothelial Cells ◽  
Dna Damage And Repair ◽  
Post Irradiation ◽  
Lethal Irradiation

Abstract In the light of the possibility that adult bone marrow cells possess hemangioblast ability, work from our laboratory demonstrates that the bone marrow sinusoids remain predominantly host-derived following bone marrow transplant when ionizing irradiation is used as the conditioning regimen. To determine the effect of lethal irradiation to the host sinusoidal endothelial cells, we performed four apoptosis related assays and two cell proliferation assays on bone marrow sections at various time points during the first two weeks post-irradiation. We found: Phosphorylated H2AX was present in both hematopoietic and sinusoidal endothelial cells. However, only hematopoietic cells showed caspase-3 dependent apoptosis. Three days after radiation, some sinusoidal endothelial cells became TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay) positive, but were activated caspase-3 and ISOL (in situ oligo ligation assay) negative, suggesting non-apoptotic DNA fragmentation. TUNEL positive endothelial cells were present in non-transplanted irradiated bone marrow 7–13 days post-irradiation while after 7 days, there were almost no TUNEL positive endothelial cells in transplanted animal, demonstrating that donor cells support sinusoidal endothelial survival. In some endothelial cells, TUNEL signal was concentrated in discrete areas of the nucleus, suggesting a repair process that involves the localization and removal of damaged DNA fragments. Very few sinusoidal endothelial cells were Ki67 positive and even fewer were BrdU positive, demonstrating that endothelial cell division is not a major mechanism for the survival of bone marrow sinusoidal system after irradiation on the short term. These results demonstrate that sinusoidal endothelial cells undergo DNA damage and repair after lethal irradiation for bone marrow transplant. These results may explain, in part, why patients with impaired DNA damage/repair mechanisms have engraftment defects.

scholarly journals Uptake of chemically modified low density lipoproteins in vivo is mediated by specific endothelial cells.

1985 ◽  
Vol 100 (1) ◽  
pp. 103-117 ◽  
Author(s):  
R E Pitas ◽  
J Boyles ◽  
R W Mahley ◽  
D M Bissell
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Kupffer Cells ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Coated Pits ◽  
Sinusoidal Endothelial Cells ◽  
Modified Lipoproteins

Acetoacetylated (AcAc) and acetylated (Ac) low density lipoproteins (LDL) are rapidly cleared from the plasma (t1/2 approximately equal to 1 min). Because macrophages, Kupffer cells, and to a lesser extent, endothelial cells metabolize these modified lipoproteins in vitro, it was of interest to determine whether endothelial cells or macrophages could be responsible for the in vivo uptake of these lipoproteins. As previously reported, the liver is the predominant site of the uptake of AcAc LDL; however, we have found that the spleen, bone marrow, adrenal, and ovary also participate in this rapid clearance. A histological examination of tissue sections, undertaken after the administration of AcAc LDL or Ac LDL (labeled with either 125I or a fluorescent probe) to rats, dogs, or guinea pigs, was used to identify the specific cells binding and internalizing these lipoproteins in vivo. With both techniques, the sinusoidal endothelial cells of the liver, spleen, bone marrow, and adrenal were labeled. Less labeling was noted in the ovarian endothelia. Uptake of AcAc LDL by endothelial cells of the liver, spleen, and bone marrow was confirmed by transmission electron microscopy. These data suggest uptake through coated pits. Uptake of AcAc LDL was not observed in the endothelia of arteries (including the coronaries and aorta), veins, or capillaries of the heart, testes, kidney, brain, adipose tissue, and duodenum. Kupffer cells accounted for a maximum of 14% of the 125I-labeled AcAc LDL taken up by the liver. Isolated sinusoidal endothelial cells from the rat liver displayed saturable, high affinity binding of AcAc LDL (Kd = 2.5 X 10(-9) M at 4 degrees C), and were shown to degrade AcAc LDL 10 times more effectively than aortic endothelial cells. These data indicate that specific sinusoidal endothelial cells, not the macrophages of the reticuloendothelial system, are primarily responsible for the removal of these modified lipoproteins from the circulation in vivo.

Stabilin-1 and Stabilin-2 Are Expressed in Bone Marrow Sinusoidal Endothelial Cells and Mediate Scavenging and Cell Adhesive Functions

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1368-1368
Author(s):  
Hong Qian ◽  
Sophie Johansson ◽  
Peter McCourt ◽  
Bård Smedsrød ◽  
Marja Ekblom ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Cell Trafficking ◽  
Tissue Remodelling ◽  
Sinusoidal Endothelial Cells ◽  
Recognition Mechanism ◽  
Hek 293 ◽  
Human Embryonic Kidney Cells ◽  
Transfected Cells ◽  
Specific Recognition

Abstract Stabilin-1 and stabilin-2 have been identified as scavenging receptors in sinusoidal capillaries in some tissues, including liver and spleen. They function as endocytic receptors for SPARC and hyaluronan, respectively, and for several other ligands. In the present study, we show by real-time PCR, Western blot and immunohistochemistry that bone marrow (BM) sinusoidal endothelial cells (SECs) ubiquitously express stabilin-1 and stabilin-2. To test the ability of BM SECs to function as a scavenging endothelium, we analyzed the uptake of specific scavenger receptor ligands after intravenous injection. Accumulation of TRITC labelled formaldehyde-treated serum albumin (FSA) was observed one hour after the injection in the BM SECs. Injection of unlabelled FSA together with TRITC-FSA reduced the fluorescence in the SECs, indicating that the uptake was due to specific recognition of FSA. Likewise, FITC-conjugated advanced glycation end products (AGEs)-modified BSA accumulated in BM SECs. These two ligands are primarily cleared by the stabilins. These results suggested that bone marrow SECs have a scavenging function. Stabilin-2 has been identified as a major receptor for hyaluronan. Hyaluronan is synthesized by primitive hematopoietic cells and has been shown to influence stem and progenitor (HSPC) functions, including mobilization and homing into BM (Nilsson et al., Blood.2003;101:856). Consequently, it is possible that adhesion of hyaluronan on HSPCs to stabilin-2 is a recognition mechanism in BM SECs, directing circulating HSPCs into BM. To investigate this, we studied adhesion of mouse BM lin-Sca-1+Kit+ (LSK) HSPCs to stabilin-1 or stabilin-2 transfected human embryonic kidney cells (HEK 293 cells). We found increased adhesion of LSK cells to stabilin-2 expressing cells, as compared to stabilin-1 expressing or non-transfected cells. Notably, hyaluronidase treatment abolished the increased adhesion of the LSK cell to stabilin-2 transfected cells. These findings indicate that stabilin-2 mediates adhesion of HSPCs to bone marrow SECs. In conclusion, this study shows a novel function for BM SECs as a scavenging endothelium expressing stabilin-1 and stabilin-2. The specific function of stabilins in recognition and endocytosis of extracellular matrix molecules, including hyaluronan and SPARC (Kzhyshkowska J et al., J Cell Mol Med.2006;10:635), suggests that these receptors are involved in tissue remodelling and cell trafficking in BM. Importantly, hyaluronan-mediated binding of HSPCs to SEC stabilin-2 may be a specific recognition mechanism for HSPCs in BM sinusoids. Similarly, binding of tumour cell-associated hyaluronan by stabilin-2 might cause tumour cells in blood to halt in bone marrow, thereby increasing the likelihood for metastasis at this site.

Laminin Expression Is Necessary for Maintenance of the Vascular Hematopoietic Niche

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 217-217
Author(s):  
Pouneh Kermani ◽  
Anita Ramnarain ◽  
Raul Catena ◽  
Zu-Lin Chen ◽  
Barbara Hempstead ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Blood Cell ◽  
Basal Lamina ◽  
Peripheral Blood ◽  
Bone Marrow Failure ◽  
Sublethal Dose ◽  
Sinusoidal Endothelial Cells ◽  
And Control ◽  
Hematopoietic Niche

Abstract Abstract 217 Laminins are heterotrimeric proteins that are the backbone for all basal laminas. They provide structural support, points for focal adhesion, and biochemical feedback for nearby cells. Laminins are found in many tissues, including bone marrow and lymphoid organs, and are detected in the discontinuous basal lamina of sinusoidal blood vessels. Laminin g1 is the predominant gamma subunit found in the bone marrow and lymphoid tissues. Here we show that the continuous expression of laminin in adulthood is necessary for viability of the vascular hematopoietic niche (sinusoidal endothelial cells). In the absence of laminin, this niche fails and hematopoiesis is impaired. To determine if sinusoidal laminin expression correlates with bone marrow failure and recovery, we used a well-established model of bone marrow failure. Wild type mice were treated with a sublethal dose of 5-fluoruracil (5-FU), and bone marrow was analyzed for disruption of sinusoid architecture and endothelial cell receptor and laminin expression. As described in other studies, shortly after treatment with 5-FU, bone marrow sinusoids became disorganized and hemorrhagic, and endothelial cells lost expression of VEGFR2. In addition, sinusoids lost their laminin-containing basal lamina. These changes correlated with bone marrow failure and onset of peripheral blood pancytopenia. As the sinusoids regained normal cytoarchitecture and VEGFR2 expression was normalized, sinusoid expression of laminin also returned to basal levels. With 5-FU-induced bone marrow failure and recovery, hematopoiesis correlated with laminin expression in the vascular hematopoietic stem cell niche. To test whether laminin expression directly affects the quality of the niche and hematopoiesis, a mutant mouse line was generated in which laminin g1 expression could be deleted by brief exposure to tamoxifen (TM). Control mice were littermates that lacked the TM-responsive Cre transgene. Prior to TM treatment, adult mutant and control mice had normal peripheral blood cell counts, and there was no evidence of gene recombination in genomic DNA samples. Adult mutant and control mice were then injected with either TM or vehicle, and the peripheral blood, bone marrow, spleen, and liver were collected after three weeks. Laminin g1 genes were deleted and laminin expression was lost in bone marrow, spleen, and liver sinusoids of only the TM-treated mutant mice. These mice also became thrombocytopenic and leukopenic. Flow cytometry showed early arrest of B-lymphocyte development within the bone marrow, bone marrow sinusoids became hemorrhagic, and the normal cytoarchitecture of the sinusoids and endothelial expression of VEGFR2 were lost. All other mouse groups were unaffected. These results suggest that continuous laminin expression is necessary for support of sinusoidal endothelial cells and the vascular hematopoietic niche. Disruption of the hematopoietic microenvironment is sufficient to alter blood cell development and release into peripheral circulation. These studies support the critical role of the microenvironment and stroma in supporting hematopoiesis. Disclosures: No relevant conflicts of interest to declare.

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