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Cancers Jan 2021Interactions between malignant cells and neighboring stromal and immune cells profoundly shape cancer progression. New forms of therapies targeting these cells have... (Review)
Review
Interactions between malignant cells and neighboring stromal and immune cells profoundly shape cancer progression. New forms of therapies targeting these cells have revolutionized the treatment of cancer. However, in order to specifically address each population, it was essential to identify and understand their individual roles in interaction between malignant cells, and the formation of the tumor microenvironment (TME). In this review, we focus on the myeloid cell compartment, a prominent, and heterogeneous group populating TME, which can initially exert an anti-tumoral effect, but with time actively participate in disease progression. Macrophages, dendritic cells, neutrophils, myeloid-derived suppressor cells, mast cells, eosinophils, and basophils act alone or in concert to shape tumor cells resistance through cellular interaction and/or release of soluble factors favoring survival, proliferation, and migration of tumor cells, but also immune-escape and therapy resistance.
PubMed: 33418996
DOI: 10.3390/cancers13020165 -
Cells Apr 2022Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of... (Review)
Review
Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Here, we focus on the function of these unique ion channels in mast cells, which are leukocytes that mature from myeloid hematopoietic stem cells. The cytoplasm of these innate immune cells contains a large number of granules that comprise messenger substances, such as histamine and heparin. Mast cells, along with basophil granulocytes, play an essential role in anaphylaxis and allergic reactions by releasing inflammatory mediators. Signaling in mast cells is mainly regulated via the release of Ca from the endoplasmic reticulum as well as from acidic compartments, such as endolysosomes. For the crosstalk of these organelles TPCs seem essential. Allergic reactions and anaphylaxis were previously shown to be associated with the endolysosomal two-pore channel TPC1. The release of histamine, controlled by intracellular Ca signals, was increased upon genetic or pharmacologic TPC1 inhibition. Conversely, stimulation of TPC channel activity by one of its endogenous ligands, namely nicotinic adenine dinucleotide phosphate (NAADP) or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P), were found to trigger the release of Ca from the endolysosomes; thereby improving the effect of TPC1 on regulated mast cell degranulation. In this review we discuss the importance of TPC1 for regulating Ca homeostasis in mast cells and the overall potential of TPC1 as a pharmacological target in anti-inflammatory therapy.
Topics: Anaphylaxis; Animals; Calcium; Calcium Channels; Endosomes; Histamine; Homeostasis; NADP
PubMed: 35563771
DOI: 10.3390/cells11091465 -
Experimental Hematology Jan 2022Inflammatory and immune signals are involved in stressed hematopoiesis under myeloablation, infection, chronic inflammation, and aging. These signals also affect... (Review)
Review
Inflammatory and immune signals are involved in stressed hematopoiesis under myeloablation, infection, chronic inflammation, and aging. These signals also affect malignant pathogenesis, and the dysregulated immune environment which causes the resistance to treatment. On activation, various types of protein tyrosine kinases in the cytoplasm mediate the cascade, leading to the transcription of target genes in the nucleus. Adaptor molecules are commonly defined as proteins that lack enzymatic activity, DNA-binding or receptor functions and possess protein-protein or protein-lipid interaction domains. By binding to specific domains of signaling molecules, adaptor proteins adjust the signaling responses after the ligation of receptors of soluble factors, including cytokines, chemokines, and growth factors, as well as pattern recognition receptors such as toll-like receptors. The signal-transducing adaptor protein (STAP) family regulates various intracellular signaling pathways. These proteins have a pleckstrin homology domain in the N-terminal region and an SRC-homology 2-like domain in the central region, representing typical binding structures as adapter proteins. Following the elucidation of the effects of STAPs on terminally differentiated immune cells, such as macrophages, T cells, mast cells, and basophils, recent findings have indicated the critical roles of STAP-2 in B-cell progenitor cells in marrow under hematopoietic stress and STAP-1 and -2 in BCR-ABL-transduced leukemogenesis. In this review, we focus on the role of STAPs in the bone marrow.
Topics: Adaptor Proteins, Signal Transducing; Animals; Bone Marrow; Hematologic Neoplasms; Hematopoiesis; Humans; Phosphoproteins; Signal Transduction
PubMed: 34780812
DOI: 10.1016/j.exphem.2021.11.002 -
Seminars in Immunopathology Sep 2016Basophils and mast cells have long been known to play critical roles in allergic disease and in immunity against parasitic infection. Accumulated evidence also supports... (Review)
Review
Basophils and mast cells have long been known to play critical roles in allergic disease and in immunity against parasitic infection. Accumulated evidence also supports that basophils and mast cells have important roles in immune regulations, host defense against bacteria and viruses, and autoimmune diseases. However, origin and molecular regulation of basophil and mast cell differentiation remain incompletely understood. In this review, we focus on recent advances in the understanding of origin and molecular regulation of mouse and human basophil and mast cell development. A more complete understanding of how basophils and mast cells develop at the molecular level will lead to development of interventions that are more effective in achieving long-term success.
Topics: Animals; Basophils; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Cell Lineage; Gene Expression Regulation; Granulocyte-Macrophage Progenitor Cells; Hematopoiesis; Humans; Mast Cells; Mice; Microphthalmia-Associated Transcription Factor; Organ Specificity; Protein Binding; Transcription Factors; Transcription, Genetic
PubMed: 27126100
DOI: 10.1007/s00281-016-0562-4 -
Journal of Biomedical Optics Apr 2023Leukocytes are mainly composed of neutrophils, basophils, eosinophils, monocytes, and lymphocytes. The number and proportion of different types of leukocytes correspond...
SIGNIFICANCE
Leukocytes are mainly composed of neutrophils, basophils, eosinophils, monocytes, and lymphocytes. The number and proportion of different types of leukocytes correspond to different diseases, so an accurate segmentation of each type of leukocyte is important for the diagnosis of disease. However, the acquisition of blood cell images can be affected by external environmental factors, which can lead to variable light and darkness, complex backgrounds, and poorly characterized leukocytes.
AIM
To address the problem of complex blood cell images collected under different environments and the lack of obvious leukocyte features, a leukocyte segmentation method based on improved U-net is proposed.
APPROACH
First, adaptive histogram equalization-retinex correction was introduced for data enhancement to make the leukocyte features in the blood cell images clearer. Then, to address the problem of similarity between different types of leukocytes, convolutional block attention module is added to the four skip connections of U-net to focus the features from spatial and channel aspects, so that the network can quickly locate the high-value information of features in different channels and spaces. It avoids the problem of large amount of repeated computation of low-value information, prevents overfitting, and improves the training efficiency and generalization ability of the network. Finally, to solve the problem of class imbalance in blood cell images and to better segment the cytoplasm of leukocytes, a loss function combining focal loss and Dice loss is proposed.
RESULTS
We use the BCISC public dataset to verify the effectiveness of the proposed method. The segmentation of multiple leukocytes using the method of this paper can achieve 99.53% accuracy and 91.89% mIoU.
CONCLUSIONS
The experimental results show that the method achieves good segmentation results for lymphocytes, basophils, neutrophils, eosinophils, and monocytes.
Topics: Leukocytes; Cytoplasm; Image Processing, Computer-Assisted
PubMed: 37065646
DOI: 10.1117/1.JBO.28.4.045002 -
Advances in Experimental Medicine and... 2011This chapter summarizes the evidence for localized signaling domains in mast cells and basophils, with a particular focus on the high affinity IgE receptor, FcεRI and... (Review)
Review
This chapter summarizes the evidence for localized signaling domains in mast cells and basophils, with a particular focus on the high affinity IgE receptor, FcεRI and its crosstalk with other membrane proteins. It is noteworthy that a literature spanning 30 years established the FcεRI as a model receptor for studying activation-induced changes in receptor diffusion and lipid raft association. Now a combination of high resolution microscopy methods, including immunoelectron microscopy and sophisticated fluorescence-based techniques, provide new insight into the nanoscale spatial and temporal aspects of receptor topography on the mast cell plasma membrane. Physical crosslinking of FcεRI with multivalent ligands leads to formation of IgE receptor clusters, termed "signaling patches," that recruit downstream signaling molecules. However, classes of receptors that engage solely withmono valent ligands can also form distinctive signaling patches. The dynamic relationships between receptor diffusion, aggregation state, clustering, signal initiation and signal strength are discussed in the context of these recent findings.
Topics: Animals; Humans; Mast Cells; Microscopy, Immunoelectron; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 21713653
DOI: 10.1007/978-1-4419-9533-9_6 -
Glycobiology Jun 2016As a physician-scientist, I have pursued research related to translational immunology with the goal of improving our ability to diagnose and treat allergic, immunologic... (Review)
Review
As a physician-scientist, I have pursued research related to translational immunology with the goal of improving our ability to diagnose and treat allergic, immunologic and other diseases involving eosinophils, basophils and mast cells. We have tried to delineate novel mechanisms of human disease, working whenever possible with primary human cells and tissues, attempting to identify targets that might be amenable to the development of new therapies. As a general strategy, we have compared eosinophils, basophils, mast cells and neutrophils to look for pathways in inflammation that were unique to distinct subsets of these cells. In doing so, the concepts of glycobiology did not enter my mind until we began noticing some intriguing functional differences involving selectins and their ligands among these cell types. One simple observation, that neutrophils were coated with a glycan that allowed them to interact with an endothelial adhesion molecule while eosinophils lacked this structure, pried open the glyco-door for me. Fruitful collaborations with card-carrying glycobiologists soon followed that have forever positively influenced our science, and have enhanced our hypotheses, experimental design, research opportunities and discoveries. Within a few years, we helped to discover Siglec-8, an I-type lectin expressed only on human eosinophils, basophils, mast cells. This receptor, together with its closest mouse counterpart Siglec-F, has been the primary focus of our work now for over a decade. If not for those in the fields of glycobiology and glycoimmunology, my lab would not have made much progress toward the goal of leveraging Siglec-8 for therapeutic purposes.
Topics: Animals; Anti-Allergic Agents; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, Myelomonocytic; Basophils; Eosinophils; Gene Expression Regulation; Glycomics; Humans; Hypersensitivity; Inflammation; Lectins; Ligands; Mast Cells; Mice; Molecular Targeted Therapy; Neutrophils; Polysaccharides; Sialic Acid Binding Immunoglobulin-like Lectins
PubMed: 26911285
DOI: 10.1093/glycob/cww024 -
Molecules (Basel, Switzerland) Feb 2018During recent decades, the market for peptide-based drugs, including antimicrobial peptides, has vastly extended and evolved. These drugs can be useful in treatment of... (Review)
Review
During recent decades, the market for peptide-based drugs, including antimicrobial peptides, has vastly extended and evolved. These drugs can be useful in treatment of various types of disorders, e.g., cancer, autoimmune diseases, infections, and non-healing wounds. Although peptides are less immunogenic than other biologic therapeutics, they can still induce immune responses and cause allergies. It is important to evaluate the immunogenic and allergic potential of peptides before they are forwarded to the expensive stages of clinical trials. The process of the evaluation of immunogenicity and cytotoxicity is complicated, as in vitro models and bioinformatics tools cannot fully simulate situations in the clinic. Nevertheless, several potentially promising tests for the preclinical evaluation of peptide drugs have been implemented (e.g., cytotoxicity assays, the basophil activation test, and lymphocyte activation assays). In this review, we focus on strategies for evaluation of the allergic potential of peptide-based therapeutics.
Topics: Allergens; Anti-Bacterial Agents; Basophils; Dermatology; Humans; Hypersensitivity; Immunity, Cellular; Lymphocyte Activation; Peptides
PubMed: 29443886
DOI: 10.3390/molecules23020414 -
Frontiers in Cell and Developmental... 2023Cerebral amyloid angiopathy (CAA) is a kind of disease in which amyloid β (Aβ) and other amyloid protein deposits in the cerebral cortex and the small blood vessels of... (Review)
Review
Cerebral amyloid angiopathy (CAA) is a kind of disease in which amyloid β (Aβ) and other amyloid protein deposits in the cerebral cortex and the small blood vessels of the brain, causing cerebrovascular and brain parenchymal damage. CAA patients are often accompanied by cardiac injury, involving Aβ, tau and transthyroxine amyloid (ATTR). Aβ is the main injury factor of CAA, which can accelerate the formation of coronary artery atherosclerosis, aortic valve osteogenesis calcification and cardiomyocytes basophilic degeneration. In the early stage of CAA (pre-stroke), the accompanying locus coeruleus (LC) amyloidosis, vasculitis and circulating Aβ will induce first hit to the heart. When the CAA progresses to an advanced stage and causes a cerebral hemorrhage, the hemorrhage leads to autonomic nervous function disturbance, catecholamine surges, and systemic inflammation reaction, which can deal the second hit to the heart. Based on the brain-heart axis, CAA and its associated cardiac injury can create a vicious cycle that accelerates the progression of each other.
PubMed: 36910141
DOI: 10.3389/fcell.2023.1156970 -
Frontiers in Immunology 2019Interleukin (IL)-33 belongs to IL-1 cytokine family which is constitutively produced from the structural and lining cells including fibroblasts, endothelial cells, and... (Review)
Review
Interleukin (IL)-33 belongs to IL-1 cytokine family which is constitutively produced from the structural and lining cells including fibroblasts, endothelial cells, and epithelial cells of skin, gastrointestinal tract, and lungs that are exposed to the environment. Different from most cytokines that are actively secreted from cells, nuclear cytokine IL-33 is passively released during cell necrosis or when tissues are damaged, suggesting that it may function as an alarmin that alerts the immune system after endothelial or epithelial cell damage during infection, physical stress, or trauma. IL-33 plays important roles in type-2 innate immunity via activation of allergic inflammation-related eosinophils, basophils, mast cells, macrophages, and group 2 innate lymphoid cells (ILC2s) through its receptor ST2. In this review, we focus on the recent advances of the underlying intercellular and intracellular mechanisms by which IL-33 can regulate the allergic inflammation in various allergic diseases including allergic asthma and atopic dermatitis. The future pharmacological strategy and application of traditional Chinese medicines targeting the IL-33/ST2 axis for anti-inflammatory therapy of allergic diseases were also discussed.
Topics: Humans; Hypersensitivity; Immunity, Innate; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Leukocytes; Medicine, Chinese Traditional
PubMed: 30886621
DOI: 10.3389/fimmu.2019.00364