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Microbiology Spectrum Aug 2016During an innate immune response, myeloid cells undergo complex morphological adaptations in response to inflammatory cues, which allow them to exit the vasculature,... (Review)
Review
During an innate immune response, myeloid cells undergo complex morphological adaptations in response to inflammatory cues, which allow them to exit the vasculature, enter the tissues, and destroy invading pathogens. The actin and microtubule cytoskeletons are central to many of the most essential cellular functions including cell division, cell morphology, migration, intracellular trafficking, and signaling. Cytoskeletal structure and regulation are crucial for many myeloid cell functions, which require rapid and dynamic responses to extracellular signals. In this chapter, we review the roles of the actin and microtubule cytoskeletons in myeloid cells, focusing primarily on their roles in chemotaxis and phagocytosis. The role of myeloid cell cytoskeletal defects in hematological disorders is highlighted throughout.
Topics: Animals; Chemotaxis; Cytoskeleton; Humans; Immunity, Innate; Myeloid Cells; Phagocytosis
PubMed: 27726772
DOI: 10.1128/microbiolspec.MCHD-0029-2016 -
Leukemia & Lymphoma Oct 2003Retinoic acid-induced terminal differentiation of myeloid cells involves the sequential regulation of cell cycle regulatory genes, coordinating the process of... (Review)
Review
Retinoic acid-induced terminal differentiation of myeloid cells involves the sequential regulation of cell cycle regulatory genes, coordinating the process of differentiation with arrest in the G0/G1 phase of the cell cycle. In this review we have summarized changes in expression and activity of cell cycle regulatory proteins associated with retinoic acid induced-growth arrest in human myeloid cell lines. These changes involve: (i) an early down-regulation of c-Myc; (ii) up-regulation of p21CIP1 and p27KIP1 and, in some cases, p15INK4b or p18INK4c; (iii) down-regulation of cyclin E and cyclin D1/D3, and, at later stages, cyclin A and cyclin B; and (iv) decreased CDK activity and dephosphorylation of pRb.
Topics: Antineoplastic Agents; Cell Cycle; Cell Cycle Proteins; Cell Differentiation; Down-Regulation; Humans; Myeloid Cells; Tretinoin
PubMed: 14692514
DOI: 10.1080/1042819031000083316 -
Infection and Immunity Apr 2017Myeloid progenitor-derived suppressor cells (MDSCs) arise from myeloid progenitors and suppress both innate and adaptive immunity. MDSCs expand during the later phases...
Myeloid progenitor-derived suppressor cells (MDSCs) arise from myeloid progenitors and suppress both innate and adaptive immunity. MDSCs expand during the later phases of sepsis in mice, promote immunosuppression, and reduce survival. Here, we report that the myeloid differentiation-related transcription factor nuclear factor I-A (NFI-A) controls MDSC expansion during sepsis and impacts survival. Unlike MDSCs, myeloid cells with conditional deletion of the gene normally differentiated into effector cells during sepsis, cleared infecting bacteria, and did not express immunosuppressive mediators. In contrast, ectopic expression of NFI-A in myeloid progenitors from NFI-A myeloid cell-deficient mice impeded myeloid cell maturation and promoted immune repressor function. Importantly, surviving septic mice with conditionally deficient NFI-A myeloid cells were able to respond to challenge with bacterial endotoxin by mounting an acute inflammatory response. Together, these results support the concept of NFI-A as a master molecular transcriptome switch that controls myeloid cell differentiation and maturation and that malfunction of this switch during sepsis promotes MDSC expansion that adversely impacts sepsis outcome.
Topics: Animals; Biomarkers; Cytokines; Disease Models, Animal; Female; Gene Targeting; Genetic Vectors; Immunity; Immunomodulation; Immunophenotyping; Leukocyte Count; Leukocytes; Lipopolysaccharides; Male; Mice; Mice, Knockout; Myeloid Cells; Myeloid-Derived Suppressor Cells; NFI Transcription Factors; Phenotype; Sepsis
PubMed: 28167668
DOI: 10.1128/IAI.00066-17 -
International Journal of Molecular... Dec 2016Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding... (Review)
Review
Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as "assistants" in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several 'checkpoints' from the blood to their destination in the brain parenchyma. As important components of the neurovascular unit, the functional state changes associated with lineage heterogeneity of myeloid cells are increasingly recognized as important for disease progression. In this review, we discuss some of the cellular elements associated with formation and function of the neurovascular unit, and present an update on the impact of myeloid cells on central nervous system (CNS) diseases in the laboratory and the clinic. We then discuss emerging strategies for harnessing the potential of site-directed myeloid cell homing to the CNS, and identify promising avenues for future research, with particular emphasis on the importance of untangling the functional heterogeneity within existing myeloid subsets.
Topics: Animals; Brain; Cell Movement; Homeostasis; Humans; Models, Biological; Myeloid Cells; Translational Research, Biomedical
PubMed: 27918464
DOI: 10.3390/ijms17122030 -
Virchows Archiv : An International... Jun 2022Transient abnormal myelopoiesis (TAM), also known as transient myeloproliferative disorder or transient leukemia, is a self-regressing neoplasia that afflicts infants...
Transient abnormal myelopoiesis (TAM), also known as transient myeloproliferative disorder or transient leukemia, is a self-regressing neoplasia that afflicts infants with trisomy 21. A recent review article documented "myeloid cell thrombus (MCT)" and "fetal vascular malperfusion (FVM)" in placentas with TAM, although the characteristic TAM placental findings have not been clarified. Here, we compared the clinical and pathological placental findings between trisomy 21 patients with or without TAM. In 13 cases of trisomy 21, we identified six placentas with TAM and seven placentas without TAM. The six placentas with TAM included two stillborn cases. Microscopically, MCT was noted in all the cases, and a high incidence of FVM (50%) was observed in TAM cases. Immunohistochemically, MCT was found to be a platelet-rich thrombus. The placentas were grouped according to the presence or absence of TAM and subsequently compared. Clinically, the incidences of abnormal fetal heart rate pattern and fetal or neonatal death were significantly higher in TAM cases. Pathologically, placenta in TAM cases weighted more than those in cases without TAM, and the incidence of MCT was significantly higher in placentas with TAM. Moreover, the incidence of FVM was higher in placentas with TAM, but this difference was not statistically significant. We propose that MCT is a diagnostic feature of placentas with TAM and may be associated with poor fetal outcomes.
Topics: Down Syndrome; Female; Humans; Infant; Infant, Newborn; Leukemoid Reaction; Myeloid Cells; Placenta; Pregnancy; Thrombosis
PubMed: 35199205
DOI: 10.1007/s00428-022-03289-5 -
Current Opinion in Virology Apr 2017Alphaviruses are medically important mosquito-borne viruses that cause a range of diseases in humans from febrile illness to arthritis or encephalitis. The innate immune... (Review)
Review
Alphaviruses are medically important mosquito-borne viruses that cause a range of diseases in humans from febrile illness to arthritis or encephalitis. The innate immune response functions to suppress virus replication through upregulation of antiviral molecules and contributes to development of the adaptive immune response. Myeloid cells act as master regulators of virus infection by initiating both the innate and adaptive immune responses. Alphaviruses are capable of antagonizing individual components of these responses to increase replicative fitness in vivo. However, recently, studies have demonstrated that some alphaviruses avoid myeloid cell replication altogether to achieve a similar effect. In this review, we summarize how alphaviruses evade myeloid cell infection and individual inductive mechanisms, thereby limiting the activation of the innate immune response.
Topics: Adaptive Immunity; Alphavirus; Animals; Cell Proliferation; Host-Pathogen Interactions; Humans; Immune Evasion; Immunity, Innate; Myeloid Cells
PubMed: 28288385
DOI: 10.1016/j.coviro.2017.02.004 -
Development (Cambridge, England) Mar 2014Much of the focus in muscle regeneration has been placed on the identification and delivery of stem cells to promote regenerative capacity. As those efforts have... (Review)
Review
Much of the focus in muscle regeneration has been placed on the identification and delivery of stem cells to promote regenerative capacity. As those efforts have advanced, we have learned that complex features of the microenvironment in which regeneration occurs can determine success or failure. The immune system is an important contributor to that complexity and can determine the extent to which muscle regeneration succeeds. Immune cells of the myeloid lineage play major regulatory roles in tissue regeneration through two general, inductive mechanisms: instructive mechanisms that act directly on muscle cells; and permissive mechanisms that act indirectly to influence regeneration by modulating angiogenesis and fibrosis. In this article, recent discoveries that identify inductive actions of specific populations of myeloid cells on muscle regeneration are presented, with an emphasis on how processes in muscle and myeloid cells are co-regulated.
Topics: Animals; Cell Lineage; Cytokines; Fibrosis; Humans; Inflammation; Macrophages; Models, Biological; Muscle Development; Muscle, Skeletal; Myeloid Cells; Regeneration; Signal Transduction
PubMed: 24595286
DOI: 10.1242/dev.098285 -
Advanced Materials (Deerfield Beach,... Apr 2024Following the success of the dendritic cell (DC) vaccine, the cell-based tumor vaccine shows its promise as a vaccination strategy. Except for DC cells, targeting other...
Following the success of the dendritic cell (DC) vaccine, the cell-based tumor vaccine shows its promise as a vaccination strategy. Except for DC cells, targeting other immune cells, especially myeloid cells, is expected to address currently unmet clinical needs (e.g., tumor types, safety issues such as cytokine storms, and therapeutic benefits). Here, it is shown that an in situ injected macroporous myeloid cell adoptive scaffold (MAS) not only actively delivers antigens (Ags) that are triggered by scaffold-infiltrating cell surface thiol groups but also releases granulocyte-macrophage colony-stimulating factor and other adjuvant combos. Consequently, this promotes cell differentiation, activation, and migration from the produced monocyte and DC vaccines (MASVax) to stimulate antitumor T-cell immunity. Neoantigen-based MASVax combined with immune checkpoint blockade induces rejection of established tumors and long-term immune protection. The combined depletion of immunosuppressive myeloid cells further enhances the efficacy of MASVax, indicating the potential of myeloid cell-based therapies for immune enhancement and normalization treatment of cancer.
Topics: Humans; Cancer Vaccines; Neoplasms; Vaccination; Cell Engineering; Myeloid Cells; Dendritic Cells
PubMed: 38295870
DOI: 10.1002/adma.202308155 -
Critical Reviews in Oncology/hematology Jun 2024In the tumor microenvironment (TME), myeloid cells play a pivotal role. Myeloid-derived immunosuppressive cells, including tumor-associated macrophages (TAMs) and... (Review)
Review
In the tumor microenvironment (TME), myeloid cells play a pivotal role. Myeloid-derived immunosuppressive cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), are central components in shaping the immunosuppressive milieu of the tumor. Within the TME, a majority of TAMs assume an M2 phenotype, characterized by their pro-tumoral activity. These cells promote tumor cell growth, angiogenesis, invasion, and migration. In contrast, M1 macrophages, under appropriate activation conditions, exhibit cytotoxic capabilities against cancer cells. However, an excessive M1 response may lead to pro-tumoral inflammation. As a result, myeloid cells have emerged as crucial targets in cancer therapy. This review concentrates on gastrointestinal tumors, detailing methods for targeting macrophages to enhance tumor radiotherapy and immunotherapy sensitivity. We specifically delve into monocytes and tumor-associated macrophages' various functions, establishing an immunosuppressive microenvironment, promoting tumorigenic inflammation, and fostering neovascularization and stromal remodeling. Additionally, we examine combination therapeutic strategies.
Topics: Humans; Gastrointestinal Neoplasms; Tumor Microenvironment; Drug Resistance, Neoplasm; Myeloid-Derived Suppressor Cells; Animals; Tumor-Associated Macrophages; Myeloid Cells; Immunotherapy; Cell- and Tissue-Based Therapy
PubMed: 38614267
DOI: 10.1016/j.critrevonc.2024.104362 -
Physiological Reviews Apr 2018The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and... (Review)
Review
The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility. Also, Bv8/PROK2 is strongly upregulated in neutrophils and other inflammatory cells in response to granulocyte-colony stimulating factor or other myeloid growth factors and functions as a pronociceptive mediator in inflamed tissues as well as a regulator of myeloid cell-dependent tumor angiogenesis. Bv8/PROK2 has been also implicated in neuropathic pain. Anti-Bv8/PROK2 antibodies or small molecule PKR inhibitors ameliorate pain arising from tissue injury and inhibit angiogenesis and inflammation associated with tumors or some autoimmune disorders.
Topics: Animals; Cell Movement; Humans; Inflammation; Inflammation Mediators; Myeloid Cells; Neurotransmitter Agents; Receptors, G-Protein-Coupled
PubMed: 29537336
DOI: 10.1152/physrev.00012.2017