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Hematopoietic Precursors (hematopoietic + precursor)
Selected AbstractsTNF-, induces the generation of Langerin/(CD207)+ immature Langerhans-type dendritic cells from both CD14,CD1a, and CD14+CD1a, precursors derived from CD34+ cord blood cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003Jean-François Arrighi Abstract CD34+ cell-derived hematopoietic precursors amplified with FLT3-ligand, thrombopoietin and stem cell factor became, after a 6-day induction with GM-CSF, IL-4 and TGF-,1, HLA-DR+, CD1a+, CD83,, CD86,, CD80, cells. A fraction of them expressed Langerin, Lag, and E-cadherin, resembling epidermal Langerhans cells (LC). TNF-, addedfor the last 3,days only marginally induced CD83 expression, but strikingly increased the proportion of immature Langerin+CD83, LC. Langerin+CD83+ and Langerin+CD83, cells were functionally distinct, the former internalizing less efficiently Langerin than the latter. Both CD1a,CD14, and CD1a,CD14+ cells sorted from FLT3-ligand, thrombopoietin and stem cell factor cultures responded to TNF-, by an increase of Langerin+ cells. Thus, TNF-, rescued LC precursors irrespective of their commitment to the monocytic lineage. When added to GM-CSF, IL-4 and TGF,,1 containing-cultures, LPS or IL-1, also induced significant numbers of Langerin+CD83, immature cells displaying a low allostimulatory activity, while CD40-ligand largely promoted highly allostimulatory Langerin,CD83+ cells. Altogether, these data show that in contrast to CD40-ligand, which induced LC maturation even in presence of TGF-,1, nonspecific proinflammatory factors such as TNF-,, IL-1, or LPS, essentially induced immature LC generation, and little cell activation in the presence of TGF-,1. [source] Effects of aging on early B- and T-cell developmentIMMUNOLOGICAL REVIEWS, Issue 1 2005Hyeyoung Min Summary:, Lymphocyte production in the bone marrow and the thymus is reduced during aging, but why this decline occurs has not been fully elucidated. The ability to isolate hematopoietic stem and progenitor cells using sophisticated flow cytometric strategies and to manipulate them in vitro and in vivo has provided insights into the effects of aging on primary lymphopoiesis. These analyses have showed that intrinsic changes in hematopoietic precursors that affect their proliferative potential are one factor that contributes to the age-related decline in B- and T-cell production. This and other age-related defects may be exacerbated by changes in the lymphopoietic support potential of the bone marrow and thymic microenvironments as well as by age-induced fluctuations in the production of various endocrine hormones. Particular attention with regard to the latter point has focused on changes in the production of sex steroids, growth hormone, and insulin-like growth factor-I. The present review summarizes recent studies of how age-related perturbations affect primary lymphopoiesis and highlights how the data necessitate the reevaluation of a number of existing paradigms. [source] Metabolic Acidosis Stimulates RANKL RNA Expression in Bone Through a Cyclo-oxygenase-Dependent Mechanism,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2003Kevin K Frick Abstract Metabolic acidosis inhibits osteoblastic bone formation and stimulates osteoclastic resorption. To determine whether acidosis alters expression of RNA for the osteoclastic differentiation factor RANKL, mouse calvariae were incubated in neutral or physiologically acidic media. Acidosis resulted in a significant cyclo-oxygenase-dependent increase in RANKL RNA levels, which would be expected to induce the associated increase in bone resorption. Introduction: Metabolic acidosis increases net calcium efflux from bone, initially through physicochemical mechanisms and later through predominantly cell-mediated mechanisms. Acidosis decreases osteoblastic bone formation and increases osteoclastic resorption. The growth and maturation of osteoclasts, derived from hematopoietic precursors in the monocyte/macrophage lineage, are dependent on the interplay of a number of factors. Commitment of pre-osteoclasts to osteoclasts is induced by the interaction of the osteoclastic cell-surface receptor RANK with a ligand expressed by osteoblasts, RANKL. The RANK/RANKL interaction not only initiates a differentiation cascade that culminates in mature bone-resorbing osteoclasts but also increases osteoclastic resorptive capacity and survival. Methods: To test the hypothesis that metabolic acidosis increases expression of RANKL, we cultured neonatal mouse calvariae in acidic (initial medium pH ,7.1 and [HCO3,] ,11 mM) or neutral (initial medium pH ,7.5 and [HCO3,] ,25 mM) medium for 24 and 48 h. We determined the relative expression of RANKL RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitated the expression by Northern analysis. Results: In this model of metabolic acidosis, there was significantly increased expression of RANKL RNA at both 24 (2-fold) and 48 h (5-fold) compared with respective controls. Net calcium efflux from bone was also increased in acidic medium compared with control medium. At 48 h, net calcium efflux correlated directly with RANKL expression (r = 0.77, n = 15, p < 0.001). Inhibition of prostaglandin synthesis with indomethacin blocked the acid-induced increase in RANKL RNA as well as the increased calcium efflux. Conclusions: Metabolic acidosis induces osteoblastic prostaglandin synthesis, followed by autocrine or paracrine induction of RANKL. This increase in RANKL would be expected to augment osteoclastic bone resorption and help explain the increase in cell-mediated net calcium efflux. [source] Indapamide, a Thiazide-Like Diuretic, Decreases Bone Resorption In VitroJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2001Agnes Lalande Abstract We recently showed that indapamide (IDP), a thiazide-related diuretic, increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium. In the present study, we evaluated the in vitro effects of this diuretic on bone cells, as well as those of hydrochlorothiazide (HCTZ), the reference thiazide, and acetazolamide (AZ), a carbonic anhydrase (CA) inhibitor. We showed that 10,4 M IDP and 10,4 M AZ, as well as 10,5 M pamidronate (APD), decreased bone resorption in organ cultures and in cocultures of osteoblast-like cells and bone marrow cells in the presence of 10,8 M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We investigated the mechanism of this antiresorptive effect of IDP; IDP decreased osteoclast differentiation as the number of osteoclasts developing in coculture of marrow and osteoblast-like cells was decreased markedly. We then investigated whether IDP affected osteoblast-like cells because these cells are involved in the osteoclast differentiation. Indeed, IDP increased osteoblast-like cell proliferation and alkaline phosphatase (ALP) expression. Nevertheless, it did not modify the colony-stimulating factor 1 (CSF-1) production by these cells. In addition, osteoblast-like cells expressed the Na+/Cl, cotransporter that is necessary for the renal action of thiazide diuretics, but IDP inhibited bone resorption in mice lacking this cotransporter, so the inhibition of bone resorption and osteoclast differentiation did not involve this pathway. Thus, we hypothesized that IDP may act directly on cells of the osteoclast lineage. We observed that resorption pits produced by spleen cells cultured in the presence of soluble osteoclast differentiation factor (sODF) and CSF-1 were decreased by 10,4 M IDP as well as 10,5 M APD. In conclusion, in vitro IDP increased osteoblast proliferation and decreased bone resorption at least in part by decreasing osteoclast differentiation via a direct effect on hematopoietic precursors. [source] Runx1, c-Myb, and C/EBP, couple differentiation to proliferation or growth arrest during hematopoiesisJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2002Alan D. Friedman Abstract Immature hematopoietic precursors proliferate as they differentiate, whereas terminal differentiation is associated with cell cycle arrest. Stem cell lineage commitment and subseqent maturation is regulated predominantly by transcription factors. Runx1 and c-Myb act in early stage hematopoietic cells to both stimulate proliferation and differentiation, whereas C/EBP,, and perhaps other C/EBP family members, block progression from G1 to S and induce terminal maturation. Coupling of differentiation to either proliferation or growth arrest by transcription factors is likely an important regulatory mechanism in multiple developmental systems. J. Cell. Biochem. 86: 624,629, 2002. © 2002 Wiley-Liss, Inc. [source] | ||||||||||