scholarly journals Akt+ IKKα/β+ Rab5+ Signalosome Mediate the Endosomal Recruitment of Sec61 and Contribute to Cross-Presentation in Bone Marrow Precursor Cells

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 539
Author(s):  
Dan Dan Xu ◽  
Chun Fang Hu ◽  
Xiang You ◽  
Nan Nan Lu ◽  
Feng Guang Gao
Keyword(s):  
Bone Marrow ◽  
Protein Kinase B ◽  
Precursor Cells ◽  
Akt Phosphorylation ◽  
Cross Presentation ◽  
Superior Efficacy ◽  
Bone Marrow Precursor ◽  
Endoplasmic Reticulum Protein ◽  
I Kappa B Kinase ◽  
Free Antigen

Cross-presentation in dendritic cells (DC) requires the endosomal relocations of internalized antigens and the endoplasmic reticulum protein Sec61. Despite the fact that endotoxin-containing pathogen and endotoxin-free antigen have different effects on protein kinase B (Akt) and I-kappa B Kinase α/β (IKKα/β) activation, the exact roles of Akt phosphorylation, IKKα or IKKβ activation in endotoxin-containing pathogen-derived cross-presentation are poorly understood. In this study, endotoxin-free ovalbumin supplemented with endotoxin was used as a model pathogen. We investigated the effects of endotoxin-containing pathogen and endotoxin-free antigen on Akt phosphorylation, IKKα/β activation, and explored the mechanisms that the endotoxin-containing pathogen orchestrating the endosomal recruitment of Sec61 of the cross-presentation in bone marrow precursor cells (BMPC). We demonstrated that endotoxin-containing pathogen and endotoxin-free antigen efficiently induced the phosphorylation of Akt-IKKα/β and Akt-IKKα, respectively. Endotoxin-containing pathogen derived Akt+ IKKα/β+ Rab5+ signalosome, together with augmented the recruitment of Sec61 toward endosome, lead to the increased cross-presentation in BMPC. Importantly, the endosomal recruitment of Sec61 was partly mediated by the formation of Akt+ IKKα/β+ signalosome. Thus, these data suggest that Akt+ IKKα/β+ Rab5+ signalosome contribute to endotoxin-containing pathogen-induced the endosomal recruitment of Sec61 and the superior efficacy of cross-presentation in BMPC.

scholarly journals Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells

2011 ◽  
Vol 26 (4) ◽  
pp. 704-717 ◽  
Author(s):  
Jochen Schulze ◽  
Thomas Bickert ◽  
F Timo Beil ◽  
Mario M Zaiss ◽  
Joachim Albers ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteoclast Formation ◽  
Precursor Cells ◽  
Interleukin 33 ◽  
Bone Marrow Precursor

Poly(I:C) induce bone marrow precursor cells into myeloid-derived suppressor cells

2011 ◽  
Vol 358 (1-2) ◽  
pp. 317-323 ◽  
Author(s):  
Cong Liu ◽  
Chaoxiong Zhang ◽  
Hongjuan Lu ◽  
Jianming Cai ◽  
Zhigang Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Suppressor Cells ◽  
Precursor Cells ◽  
Poly I:C ◽  
Myeloid Derived Suppressor Cells ◽  
Bone Marrow Precursor

Cbl-Deficient Mice Display Erythropoietin Hypersensitivity and Enhanced Phosphorylation of Protein Kinase B/Akt.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3137-3137
Author(s):  
Terri D. Richmond ◽  
Monica L. Bailey ◽  
Wallace Y. Langdon ◽  
Dwayne L. Barber
Keyword(s):  
Bone Marrow ◽  
Protein Kinase ◽  
Cell Survival ◽  
De Novo ◽  
Protein Kinase B ◽  
Negative Regulator ◽  
Erythroid Cell ◽  
Akt Phosphorylation ◽  
Deficient Mice

Abstract Erythropoietin (EPO) is the primary cytokine regulator of erythropoiesis, stimulating growth, preventing apoptosis, and promoting differentiation of red blood cell progenitors. The critical importance of EPO, EPO receptor (EPO-R) and JAK2 to erythropoiesis is demonstrated by the fatal embryonic anemia that develops in EPO, EPO-R or JAK2 knockout mice. Intracellular signal transduction pathways regulating growth, differentiation and cell survival downstream of the EPO-R and JAK2 are well documented. However, activation of the EPO-R is transient and down regulated by several negative regulators including tyrosine phosphatases, inositol phosphatases and ubiquitin ligases. The negative regulator, Cbl, has been implicated as a tumour suppressor in murine sarcoma, B cell leukemia, and erythroleukemia. More recently, Cbl was found in a de novo form of acute myeloid leukemia and has been implicated in the formation of gastric tumours. Cbl is known to bind, ubiquitinate, and downregulate signaling from numerous activated hematopoietic and non-hematopoietic receptors. The discovery that Cbl is a target of EPO-dependent tyrosine phosphorylation, together with the finding that the EPO-R is ubiquitinated in vivo, led us to hypothesize that Cbl deficiency leads to altered murine erythropoiesis. Resting C57Bl/6 Cbl-/- mice display normal hematologic parameters with the exception of an increased platelet count. However, Cbl deficient mice respond to phenylhydrazine-mediated anemia with increased reticulocyte production and hematocrit recovery. The hypersensitivity of Cbl deficient mice to anemia may be explained by a three-fold enhancement of splenic colony forming unit-erythroid (CFU-E) and an overall increase in burst forming unit-erythroid (BFU-E) and CFU-E. Furthermore, the elevated sensitivity of Cbl deficient mice to anemia is echoed by increased EPO-R and protein kinase B (PKB)/Akt phosphorylation in splenic erythroblasts at high levels of EPO stimulation. Erythrocyte differentiation was examined by monitoring the expression of the erythroid markers CD71 (Transferrin Receptor) and Ter119. Cbl deficient mice do not have significantly more proerythroblasts than wild-type mice. Interestingly, Cbl deficient mice show impaired erythroid maturation with a 1.7 fold decrease in orthochromatophilic erythroblast levels, elevated erythroid apoptosis in the bone marrow, and no compensation by splenic erythroblast production. These data (as well as earlier studies from our laboratory with STAT1-/- and SHIP-1-/- mice) illustrate the remarkable ability of the spleen to compensate for alterations in bone marrow erythropoiesis. It also suggests that Cbl regulates pathway(s) associated with regulation of erythroid cell survival through regulation of the PI 3 kinase, PKB/Akt signaling cascade.

scholarly journals Enrichment and characterization of thymus-repopulating cells in stroma-dependent cultures of rat bone marrow

1993 ◽  
Vol 104 (4) ◽  
pp. 1039-1048
Author(s):  
Z. Prakapas ◽  
M. Denoyelle ◽  
C. Dargemont ◽  
F.G. Kroese ◽  
J.P. Thiery ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Precursor Cells ◽  
Response Analysis ◽  
Mouse Bone Marrow ◽  
Low Density ◽  
Short Term ◽  
Fetal Mouse ◽  
Bone Marrow Precursor ◽  
Rat Bone

The bone marrow precursor cells seeding the thymus have been difficult to investigate using fresh bone marrow and in vivo thymus reconstitution assays. We have therefore designed a short-term bone marrow culture system allowing the study of thymus-repopulating cells in the marrow microenvironment. Low-density rat bone marrow cells were grown on pre-established mouse bone marrow stromal cell layers. Cocultured cells were maintained either under steroid-free conditions (Whitlock/Witte-type culture) or in the presence of 10(−7) M hydrocortisone (Dexter-type culture). After 3 days in vitro, the unanchored cell fractions were tested for their ability to colonize and repopulate fetal mouse thymic lobes in vitro. Both fresh low-density cells and Whitlock/Witte-type cultures, but not Dexter-type cultures, gave rise intrathymically to significant numbers of rat donor-type Thy-1.1high CD2+ CD5low CD43+ cells accounting for 50% to 90% of the organ-cultured cells at day 14. Repopulation of fetal mouse thymic lobes by rat Thy-1.1high cells could be used as a readout assay for initiation of thymopoiesis from bone marrow precursor cells, since 90% of the cells were CD3-/low and TCR alpha beta-/low and 15% of the cells co-expressed CD4 and CD8. Dose-response analysis showed that thymus repopulating cells were at least maintained, if not amplified during the 3-day culture period, leading to at least a 10-fold enrichment as compared to unfractionated bone marrow. Unlike fresh low-density cells before culture, short-term Whitlock/Witte-type cultures were depleted in myeloid-restricted precursor cells. In culture, the thymus-repopulating activity was predominantly associated with a 10% lymphoid cell subset which did not express the B-lineage-associated antigens revealed by HIS24 (the rat B220 equivalent) and HIS50 mAbs. We propose that unanchored thymus-repopulating cells enriched in Whitlock/Witte-type cultures may represent lymphoid-restricted, T-cell precursors of the bone marrow capable of emigrating and colonizing the thymus.

scholarly journals Paclitaxel and CYC3, an aurora kinase A inhibitor, synergise in pancreatic cancer cells but not bone marrow precursor cells

2012 ◽  
Vol 107 (10) ◽  
pp. 1692-1701 ◽  
Author(s):  
Y Lin ◽  
F M Richards ◽  
B-F Krippendorff ◽  
J L Bramhall ◽  
J A Harrington ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Aurora Kinase ◽  
Precursor Cells ◽  
Aurora Kinase A ◽  
Pancreatic Cancer Cells ◽  
Bone Marrow Precursor ◽  
Kinase A

scholarly journals Bone Marrow Precursor Cells from Aged Mice Generate CD4 T Cells That Function Well in Primary and Memory Responses

2008 ◽  
Vol 181 (7) ◽  
pp. 4825-4831 ◽  
Author(s):  
Sheri M. Eaton ◽  
Alexander C. Maue ◽  
Susan L. Swain ◽  
Laura Haynes
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Cd4 T Cells ◽  
Precursor Cells ◽  
Aged Mice ◽  
Bone Marrow Precursor
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