Monocyte and Multinucleated Cells

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Microenvironment".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 5668

Special Issue Editors


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Guest Editor
Transplant Immunology, The Houston Methodist Research Institute, Houston, TX 77030, USA
Interests: macrophages; actin cytoskeleton; RhoA pathway; chronic rejection; transplantation; germ cells; stem cells; Xenopus laevis; development
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Guest Editor
The Houston Methodist Research Institute, Transplant Immunology, Houston, TX 77030, USA
Interests: immunobiology; transplantation immunology; oncology; cell biology; reproductive and developmental biology

Special Issue Information

Dear Colleagues,

Monocytes are the largest of the leukocytes. They exist in all vertebrates and are produced in the bone marrow before being released into circulation. Monocytes travel from the circulation into the tissues and differentiate into macrophages and monocyte-derived dendritic cells. Monocytes are vital in the defense against pathogens and are implicated in autoimmune and inflammatory diseases. Blood monocytes have three subtypes: classical, intermediate, and non-classical. The subtypes vary in their cytokine secretion and cell surface markers.

Monocytes can fuse to form multinucleated giant cells (MGCs), such as the bone-resorbing cells osteoclasts. Osteoclast MGCs are about ~100 μm in diameter with up to 20 nuclei. Monocytes also fuse to form inflammatory MGCs, such as Langhans giant cells (LGCs) in response to M. tuberculosis infection. LGCs sequester the pathogen within the host. MGCs have been observed in breast cancer, lung cancer, gastric cancer, lymphoma, and esophageal cancer. By phagocytosing cancer cells, MGCs prevent lymph node metastasis. In response to foreign materials, such as medical implants, monocytes can fuse to form foreign body giant cells (FBGCs), which produce and release ROS in an attempt to degrade and digest a foreign material.

The formation of giant cells through monocyte fusion is still not thoroughly understood, and only a few important proteins playing a role in this process have been described. LGC and FBGC formation is initiated by different cytokines, such as IFNγ and IL-4. The monocyte fusion is activated by fusogenic stimuli, such as CCL2 and CCL3, which upregulate cell–cell adhesion proteins, such as LFA-1, ICAM-1, and E-cadherin, and upregulate fusion-facilitating proteins, such as CD200, SIRPα/CD172a/MFR, CD47, CD36, CD62E (E-selectin), matrix metallopeptidase 9 (MMP9), and dendrocyte-expressed seven transmembrane protein (DC-STAMP).

Although monocytes per se are not present in invertebrates, some invertebrates, such as clam Mercenaria mercenaria, can form multinucleated giant cells morphologically similar to Langhans cells and foreign body giant cells and they phagocytose parasites and sequester environmental pollutants. Another example is Drosophila, which has multinucleated giant hemocytes (MGHs) in the blood equivalent, hemolymph. MGHs are gigantic cells with multiple nuclei. They are highly motile and functionally similar to mammalian inflammatory MGCs by sequestering and killing pathogens/parasites.

The presence of multinuclear giant cells not only in vertebrates but also in invertebrates indicates that their formation and functions are evolutionarily ancient.

Prof. Dr. Malgorzata Kloc
Dr. Ahmed Uosef
Guest Editors

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Keywords

  • transplantation
  • macrophages
  • actin cytoskeleton
  • rejection markers
  • immune cells

Published Papers (2 papers)

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13 pages, 2774 KiB  
Article
A New Method to Sort Differentiating Osteoclasts into Defined Homogeneous Subgroups
by Philippa A. Hulley and Helen J. Knowles
Cells 2022, 11(24), 3973; https://doi.org/10.3390/cells11243973 - 08 Dec 2022
Cited by 1 | Viewed by 1773
Abstract
Osteoclasts regulate skeletal development but also drive pathological osteolysis, making them prime therapeutic targets. Osteoclast research is limited by the heterogeneity of osteoclast populations generated in vitro, where the mixture of undifferentiated monocytes, binuclear pre-osteoclasts and multinucleated osteoclasts has by necessity been considered [...] Read more.
Osteoclasts regulate skeletal development but also drive pathological osteolysis, making them prime therapeutic targets. Osteoclast research is limited by the heterogeneity of osteoclast populations generated in vitro, where the mixture of undifferentiated monocytes, binuclear pre-osteoclasts and multinucleated osteoclasts has by necessity been considered a single osteoclast population. This study describes the differentiation of primary human CD14+ monocyte-derived osteoclasts in 3D collagen gels. These osteoclasts remained small (>95% with ≤5 nuclei) but were viable and active; when released from the gel with collagenase, they fused rapidly when reseeded onto solid substrates and resorbed dentine for 2–3 weeks. 3D-generated osteoclasts expressed cell surface markers of osteoclast differentiation (e.g., CD9, RANK, OSCAR, CD63, CD51/61) which, with their small size, enabled live cell sorting of highly enriched viable subpopulations of human osteoclasts that retained full functional resorption capacity. Low-yield osteoclast preparations were strongly enriched to remove undifferentiated cells (e.g., 13.3% CD51/61+ to 84.2% CD51/61+), and subpopulations of CD9+CD51/61− early osteoclasts and CD9+CD51/61+ mature cells were distinguished. This novel approach allows the study of selected populations of differentiating osteoclasts in vitro and opens the door to in-depth transcriptomic and proteomic analysis of these cells, increasing our ability to study human osteoclast molecular mechanisms relevant to development, aging and disease. Full article
(This article belongs to the Special Issue Monocyte and Multinucleated Cells)
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Review

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19 pages, 2335 KiB  
Review
Monocytes in Tumorigenesis and Tumor Immunotherapy
by Xiaodie Chen, Yunqing Li, Houjun Xia and Youhai H. Chen
Cells 2023, 12(13), 1673; https://doi.org/10.3390/cells12131673 - 21 Jun 2023
Cited by 2 | Viewed by 3072
Abstract
Monocytes are highly plastic innate immune cells that display significant heterogeneity during homeostasis, inflammation, and tumorigenesis. Tumor-induced systemic and local microenvironmental changes influence the phenotype, differentiation, and distribution of monocytes. Meanwhile, monocytes and their related cell subsets perform an important regulatory role in [...] Read more.
Monocytes are highly plastic innate immune cells that display significant heterogeneity during homeostasis, inflammation, and tumorigenesis. Tumor-induced systemic and local microenvironmental changes influence the phenotype, differentiation, and distribution of monocytes. Meanwhile, monocytes and their related cell subsets perform an important regulatory role in the development of many cancers by affecting tumor growth or metastasis. Thanks to recent advances in single-cell technologies, the nature of monocyte heterogeneity and subset-specific functions have become increasingly clear, making it possible to systematically analyze subset-specific roles of monocytes in tumorigenesis. In this review, we discuss recent discoveries related to monocytes and tumorigenesis, and new strategies for tumor biomarker identification and anti-tumor immunotherapy. Full article
(This article belongs to the Special Issue Monocyte and Multinucleated Cells)
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