Search results for "myelopoiesis"
showing 10 items of 20 documents
Sustained telomere erosion due to increased stem cell turnover during triple autologous hematopoietic stem cell transplantation.
2007
Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results regarding the persistence of telomere shortening. Here we have prospectively studied telomere length and proliferation kinetics of hematopoietic cells in aggressive non-Hodgkin lymphoma patients who underwent a four-course high-dose chemotherapy protocol combined with triple autologous stem cell transplantation. We observed sustained telomere shortening in hematopoietic cells af…
GM-CSF Programs Hematopoietic Stem and Progenitor Cells During Candida albicans Vaccination for Protection Against Reinfection
2021
More mechanistic studies are needed to reveal the hidden details of in vivo-induced trained immunity. Here, using a Candida albicans live vaccine mouse model we show that vaccination protects mice against a secondary infection and increases the number of bone marrow, and especially, splenic trained monocytes. Moreover, vaccination expands and reprograms hematopoietic stem and progenitor cells (HSPCs) early during infection and mobilize them transiently to the spleen to produce trained macrophages. Trained HSPCs are not only primed for myeloid cell production but also reprogramed to produce a greater amount of proinflammatory cytokines in response to a second challenge. Additionally, their a…
The suppressive effects of recombinant human tumor necrosis factor‐alpha on normal and malignant myelopoiesis: Synergism with interferon‐gamma
1988
The modulation of growth of normal and leukemic myeloid progenitor cells in soft agar cultures by recombinant human tumor necrosis factor-alpha (TNF alpha) and recombinant human interferon-gamma (IFN gamma) was investigated. TNF alpha inhibited colony formation of all colony types representing different maturational stages of normal progenitor cells committed to the myeloid lineage with different orders of sensitivity. Blast-type colonies derived from patients with acute myelogenous leukemia were more sensitive to TNF alpha inhibition than progenitor cells purified from normal bone marrow or bone marrow from patients with stable-phase chronic myelogenous leukemia. The response of most colon…
The Impact of NFAT Inhibition on Neutrophil Effector Functions in Patients after Allogeneic Hematopoietic Stem Cell Transplantation and on Neutrophil…
2016
Abstract Background and Aims: Immunosuppressive medication e.g. by calcineurin inhibitors substantially contributes to the risk for opportunistic fungal infections in patients after allogeneic transplantation (HSCT). It is well known that the nuclear factor of activated T cells (NFAT) is an important transcription factor downstream of calcineurin especially in T cells. Additionally, recent data in rodent models indicate that NFAT also seems to play a relevant role in innate antifungal immune responses by polymorphonuclear neutrophils (PMN), as well as in regulation of myelopoiesis and myeloid differentiation. Methods: Firstly, isolated PMN from healthy donors were analyzed in vitro in absen…
The Impact of NFAT Inhibition on Neutrophil Antifungal Defense and Myelopoiesis in Cyclosporine A Treated and NFATc1LysM Mice
2015
Abstract Background and Aims: Immunodeficient patients after allogeneic stem cell transplantation (HSCT) are heavily threatened by opportunistic fungal infections like invasive pulmonary aspergillosis (IPA), partly due to immunosuppressive medication e.g. by calcineurin inhibitors like cyclosporine A (CsA) or tacrolimus. It is well known that the nuclear factor of activated T cells (NFAT) is an important transcription factor downstream of calcineurin in the adaptive immune system especially in T cells. Additionally, there is a growing body of evidence that NFAT also plays a substantial role in innate immune response against invasive fungal diseases by polymorphonuclear neutrophils (PMN), as…
Detection of a TLR2 agonist by hematopoietic stem and progenitor cells impacts the function of the macrophages they produce
2013
Several groups have shown that detection of microbial components by TLRs on hematopoietic stem and progenitor cells (HSPCs) instructs myeloid cell generation, raising interest in the possibility of targeting TLRs on HSPCs to boost myelopoiesis. However, although "TLR-derived" cells exhibit myeloid cell characteristics (phagocytosis, cytokine production, antigen presentation), it is not clear whether they are functionally equivalent to macrophages derived in the absence of TLR activation. Our in vitro and in vivo studies show that macrophages derived from mouse and human HSPC subsets (including stem cells) exposed to a TLR2 agonist prior to or during macrophage differentiation produce lower …
Rôle de Tif1gamma dans les différenciations granulo-monocytaire et macrophagique
2015
Chronic myelomonocytic leukemia (CMML) is a hematologic stem cell disease whose characteristics correspond to myelodysplastic/myeloproliferative syndroms (MDS/MPS). Hematopoietic conditional deletion of Tif1γ in mice leads to the development of a MDS/MPS, mimiking human CMML, when age is comprised between 6 to 10 months, defining Tif1γ as a tumour suppressor gene. Moreover, peritoneal macrophage population in these mice is decreased despite a monocytosis.The aims of my work were first to characterize in sick mice the myeloid population, and second to study macrophage differentiation. The myeloid population in Tif1γΔ/Δ mice is morphologically immature, with granulocytic and monocytic feature…
cIAP1-dependent TRAF2 degradation regulates the differentiation of monocytes into macrophages and their response to CD40 ligand.
2008
AbstractPeripheral blood monocytes are plastic cells that migrate to tissues and differentiate into various cell types, including macrophages, dendritic cells, and osteoclasts. We have described the migration of cellular inhibitor of apoptosis protein 1 (cIAP1), a member of the IAP family of proteins, from the nucleus to the Golgi apparatus in monocytes undergoing differentiation into macrophages. Here we show that, once in the cytoplasm, cIAP1 is involved in the degradation of the adaptor protein tumor necrosis factor receptor–associated factor 2 (TRAF2) by the proteosomal machinery. Inhibition of cIAP1 prevents the decrease in TRAF2 expression that characterizes macrophage formation. We d…
Supportive care of the older cancer patient
2003
Aging is associated with decreased functional reserve of multiple organ systems and with changes in the pharmacokinetics and pharmacodinamics of drugs. Older individuals express enhanced susceptibility to the complications of cytotoxic chemotherapy, especially to myleotoxicity, mucositis, cardiotoxicity and neurotoxicity. The management of older individuals with chemotherapy involves then prevention of these complications. General precautions include proper patient selection, based on the comprehensive geriatric assessment (CGA), dose adjustment for agents that are renally excreted to the patient creatinine clearance and maintenance of hemoglobin levelsor =12 g/dl. Filgrastim and pegfilgras…
Role of hematopoietic stem and progenitor cells in training immunity against infection
2022
During an infection, haematopoiesis is altered to increase the output of mature myeloid cells to fight off the pathogen. It has been demonstrated that the detection of pattern recognition receptor agonists by hematopoietic stem and progenitor cells (HSPCs) induces their differentiation towards mature myeloid cells with modified phenotypes. In the present PhD thesis, we show that an in vitro transient exposure of HSPCs to live Candida albicans cells is sufficient to induce a trained phenotype of the macrophages they produce in a dectin-1- and TLR2-dependent manner. Additionally, we use an HSPC transplantation mouse model to demonstrate that the direct interaction of β-glucans and their recep…