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Innate Immune System in Cardiovascular Diseases
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Benjamin J. Kopecky, Kory J. Lavine
Following myocardial infarction, macrophages are activated by mediators released from injured and dead cardiomyocytes, including alarmins, DAMPs, nucleic acids, and lipids [109]. Tissue-resident CCR2+ macrophages (~10–15% of the total resident macrophage population) are activated by products released by ferroptotic cardiomyocytes [110], and they signal through MYD88 (an adapter protein of TLR) to orchestrate monocyte and neutrophil recruitment through the expression of chemokines CXCL2, CXCL5, CCL2, and CCL7 and cytokines IL-1β, IL-6, and TNF [38, 39]. Mitochondrial and nuclear DNA are DAMPs recognized by TLR9 and stimulator of interferon genes (STING; expressed on resident macrophages) [38] and have been implicated in macrophage activation and heart failure [111, 112]. Myeloid-derived S100A8 and S100A9 also act as DAMPs following their release from dying immune cells and bind to receptors for advanced glycation endproducts (RAGE), resulting in NF-ĸβ signaling and amplification of a feed-forward loop driven by ongoing cytokine and DAMP release. These mediators contribute to accelerated myelopoiesis and mobilization of myeloid cells from hematopoietic tissues [113]. Recent studies have shown the ability of CCR2− macrophages to interrupt this feed-forward loop [114].
Regenerative Medicine in Pain Management
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Sharon McQuillan, Rafael Gonzalez
Bone marrow-derived stem cells are the most commonly used source and are permitted by the FDA and other governing bodies. Bone marrow aspirate has been approved and used safely for many years for the treatment of blood cancers and other hematological disorders. Bone marrow is the primary site of new blood cell production. Two main cell types are produced in bone marrow: hematopoietic cells (myelopoietic, erythropoietic, lymphocytes, plasma, reticular, monocytes, magakarocytes, hematopoietic stem cells) and stromal cells (fibroblasts, macrophages, adipocytes, osteoblasts, osteoclasts, endothelial cells, MSCs). The frequency of stem cell production decreases proportionately with age.
Quantitative Assays for Human Hemopoietic Progenitor Cells
Published in Adrian P. Gee, BONE MARROW PROCESSING and PURGING, 2020
Heather J. Sutherland, Allen C. Eaves, Connie J. Eaves
Most of the other factors now known to have hemopoietic colony-stimulating activity have been called interleukins, because they are produced by one type of leukocyte and act on another. One of these that has been intensively studied is interleukin-3 (IL-3). It is also known by a variety of other names, including “multi-CSF”, because of its potent stimulating effects on the early stages of erythroid colony development from primitive erythroid cells, as well as on pluripotent cells and precursors of other lineages.54 Now that many factors are available as recombinant, purified reagents, it is clear that most can act on a much broader range of target cell populations than originally anticipated. For example, GM-CSF and IL-3 show extensive, although not complete, overlap on the types of cells they can stimulate,55,56 and G-CSF can stimulate primitive pluripotent cells, as well as later progenitors that mature into granulocytes.57 Other glycoprotein molecules with CSF activity on human or murine myeloid progenitors include IL-5,58,59 IL-6,60 IL-7,61 IL-9,62 IL-10,63 and IL-11.64 In addition, the ability of various factors to synergize in stimulating various aspects of myelopoiesis in vitro, has revealed the importance of testing combinations of factors which may not alone appear to have much effect. IL-1, IL-4, IL-6, IL-7, IL-11, and the ligand for c-kit are examples of factors known to participate in such synergisms.34,57
Ex vivo and in vivo T-cell depletion in allogeneic transplantation: towards less or non-cytotoxic conditioning regimens
Published in Expert Review of Clinical Immunology, 2022
Rupert Handgretinger, Anne-Marie Arendt, Claus-Philipp Maier, Peter Lang
Especially for patients with nonmalignant diseases, new reduced intensity conditioning regimens must be developed and carefully investigated in clinical studies. In this review, we are proposing such new strategies, which could finally allow to ensure engraftment with minimal or even without any cytotoxic therapy. Successful allogeneic transplantations in patients with SCID have shown that this is possible in the absence of recipients‘ T-cells, although these patients have a normal myelopoiesis. It is not clear whether myeloablation to open space for a stem graft is a valid concept and a prerequisite for successful engraftment, since high rates of engraftment in nonmyeloablative or minimally myeloablated mice have been reported [84–86]. The use of high numbers of PBSCs in this context could also be of advantage to achieve long-term engraftment. Ex vivo methods for the effective depletion of donor cells have been established, and all efforts should now be made to eliminate or tolerize recipients‘ T-cells. For patients with hemoglobinopathies or other inherited disorders, minimal conditioning and allogeneic transplantation might even be superior to gene therapy with autologous stem cells, since this approach still requires an intensive myeloablative preparative regimen [87].
Transcriptomic Profiling of Circulating HLA-DR– Myeloid Cells, Compared with HLA-DR+ Myeloid Antigen-presenting Cells
Published in Immunological Investigations, 2021
Reem Saleh, Rowaida Z Taha, Varun Sasidharan Nair, Salman M Toor, Nehad M Alajez, Eyad Elkord
Immunosuppressive myeloid cells have been implicated in many pathological conditions, such as age-associated inflammation, autoimmune diseases, infections, organ transplantation, trauma, and cancer (Gabrilovich and Nagaraj 2009; Kirkwood et al. 2018). Myelopoiesis is disrupted during these pathological conditions, leading to increased levels of a heterogeneous myeloid cell population, which comprises cells halted at various stages of maturation/differentiation with a potent immunosuppressive activity, referred to as myeloid-derived suppressor cells (MDSCs) (Awad et al. 2018; Gabrilovich and Nagaraj 2009). MDSCs have a role in maintaining immune tolerance and circulate at very low levels in healthy individuals (Khaled et al. 2013). In contrast, MDSCs circulate at higher levels in disease contexts, for instance, cancer, and their numbers increase by 10-folds (Khaled et al. 2013).
Enteral broad-spectrum antibiotics antagonize the effect of fecal microbiota transplantation in preterm pigs
Published in Gut Microbes, 2021
Anders Brunse, Simone Margaard Offersen, Josefine Juliane Mosegaard, Ling Deng, Peter Damborg, Dennis Sandris Nielsen, Per Torp Sangild, Thomas Thymann, Duc Ninh Nguyen
Gut colonization influences not only mucosal immune cell compartments but also hematopoiesis,14,15 and consequently, enteral broad-spectrum AB use in the neonatal period has a large impact on developing immunity, raising concerns about both short- and long-term issues of neonatal AB exposure. In this experiment, we performed blood lymphocyte profiling and assessed blood myeloid cell function at the time of AB discontinuation and again at euthanasia. Five days after the final AB treatment, no numerical development had occurred in the circulating leukocyte pool. Moreover, AB-treated animals displayed systemic immune suppression, shown by diminished gene response and cytokine secretion following bacterial antigen challenge. This indicates the existence of a significant lag phase between gut recolonization following early enteral broad-spectrum AB treatment and subsequent immune cell expansion, and could be a window of heightened infection risk. Conversely, control animals had a transient decrease in circulating lymphocytes and neutrophils on day 5, possibly due to gut homing in response to colonization, both of which had replenished and expanded in numbers on day 9. Moreover, the phagocytic capacity of neutrophils in control animals was decreased at the late stage, indicating myelopoietic activity and recruitment of newly differentiated cells. NEC status was not associated with changes in systemic immune parameters.