scholarly journals Multinucleated Giant Cell Formation as a Portal to Chronic Bacterial Infections

2020 ◽  
Vol 8 (11) ◽  
pp. 1637
Author(s):  
Jacob L. Stockton ◽  
Alfredo G. Torres
Keyword(s):  
Burkholderia Pseudomallei ◽  
Bacterial Infections ◽  
Cell Formation ◽  
Giant Cells ◽  
Clinical Findings ◽  
Giant Cell Formation ◽  
Similarities And Differences ◽  
And Function ◽  
Multinucleated Giant Cell Formation

This review provides a snapshot of chronic bacterial infections through the lens of Burkholderia pseudomallei and detailing its ability to establish multi-nucleated giant cells (MNGC) within the host, potentially leading to the formation of pyogranulomatous lesions. We explore the role of MNGC in melioidosis disease progression and pathology by comparing the similarities and differences of melioidosis to tuberculosis, outline the concerted events in pathogenesis that lead to MNGC formation, discuss the factors that influence MNGC formation, and consider how they fit into clinical findings reported in chronic cases. Finally, we speculate about future models and techniques that can be used to delineate the mechanisms of MNGC formation and function.

scholarly journals Multinucleated Giant Cell Formation as a Portal to Chronic Bacterial Infections

2020 ◽  
Author(s):  
Jacob L. Stockton ◽  
Alfredo G. Torres
Keyword(s):  
Burkholderia Pseudomallei ◽  
Bacterial Infections ◽  
Cell Formation ◽  
Giant Cells ◽  
Clinical Findings ◽  
Giant Cell Formation ◽  
Similarities And Differences ◽  
And Function ◽  
Multinucleated Giant Cell Formation

This review provides a snapshot of chronic bacterial infections through the lens of Burkholderia pseudomallei; detailing its ability to establish multi-nucleated giant cells (MNGC) within the host, leading to the formation of pyogranulomatous lesions. We explore the role of MNGC in melioidosis disease progression and pathology by comparing the similarities and differences of melioidosis to tuberculosis, outlining the concerted events in pathogenesis that lead to MNGC formation, discussing the factors that influence MNGC formation and how they fit into clinical findings reported in chronic cases. Finally, we speculate about future models and techniques that can be used to delineate the mechanisms of MNGC formation and function.

scholarly journals Pathophysiology of Giant Cell Formation in Giant Cell Tumor and Lesions: A Review

2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Samar Khan
Keyword(s):  
Giant Cell ◽  
Cell Formation ◽  
Giant Cells ◽  
Cellular Mechanisms ◽  
Gm Csf ◽  
Current State ◽  
Giant Cell Formation ◽  
And Function ◽  
Multinucleated Giant Cell Formation ◽  
Insight Into

This review is intended to provide insight into the current state of understanding regarding the molecular and cellular mechanisms underlying the formation and function of various types of multinucleated giant cells. Present article mainly focus on various factors such as e.g. GCP/F, GM-CSF, Meltrin, MIP-1 that contribute to giant cell formation and function. This review focuses on recent efforts to develop a better understanding of the molecular and cellular biology of multinucleated giant cell formation and function.

scholarly journals A role for tetraspanin proteins in regulating fusion induced by Burkholderia thailandensis

2020 ◽  
Vol 209 (4) ◽  
pp. 473-487 ◽  
Author(s):  
Atiga Elgawidi ◽  
Muslim Idan Mohsin ◽  
Fawwaz Ali ◽  
Amyleigh Watts ◽  
Peter N. Monk ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Cell Formation ◽  
High Morbidity ◽  
Virulence Determinants ◽  
Macrophage Cell ◽  
Burkholderia Thailandensis ◽  
Bacterial Pathogenicity ◽  
Giant Cell Formation ◽  
Host Cell Factors ◽  
Multinucleated Giant Cell Formation

Abstract Burkholderia pseudomallei is the causative agent of melioidosis, a disease with high morbidity that is endemic in South East Asia and northern Australia. An unusual feature of the bacterium is its ability to induce multinucleated giant cell formation (MNGC), which appears to be related to bacterial pathogenicity. The mechanism of MNGC formation is not fully understood, but host cell factors as well as known bacterial virulence determinants are likely to contribute. Since members of the tetraspanin family of membrane proteins are involved in various types of cell:cell fusion, their role in MNGC formation induced by Burkholderia thailandensis, a mildly pathogenic species closely related to B. pseudomallei, was investigated. The effect of antibodies to tetraspanins CD9, CD81, and CD63 in MNGC formation induced by B. thailandensis in infected mouse J774.2 and RAW macrophage cell lines was assessed along with that of recombinant proteins corresponding to the large extracellular domain (EC2) of the tetraspanins. B. thailandensis-induced fusion was also examined in macrophages derived from CD9 null and corresponding WT mice, and in J774.2 macrophages over-expressing CD9. Antibodies to CD9 and CD81 promoted MNGC formation induced by B. thailandensis, whereas EC2 proteins of CD9, CD81, and CD63 inhibited MNGC formation. Enhanced MNGC formation was observed in CD9 null macrophages, whereas a decrease in MNGC formation was associated with overexpression of CD9. Overall our findings show that tetraspanins are involved in MNGC formation induced by B. thailandensis and by implication, B. pseudomallei, with CD9 and CD81 acting as negative regulators of this process.

High-Temperature Sintering of Xenogeneic Bone Substitutes Leads to Increased Multinucleated Giant Cell Formation: In Vivo and Preliminary Clinical Results

2015 ◽  
Vol 41 (5) ◽  
pp. e212-e222 ◽  
Author(s):  
Mike Barbeck ◽  
Samuel Udeabor ◽  
Jonas Lorenz ◽  
Markus Schlee ◽  
Marzellus Grosse Holthaus ◽  
...  
Keyword(s):  
High Temperature ◽  
Inflammatory Response ◽  
Giant Cell ◽  
Multinucleated Giant Cell ◽  
Cell Formation ◽  
Giant Cells ◽  
Clinical Aspects ◽  
Multinucleated Giant Cells ◽  
Giant Cell Formation ◽  
Multinucleated Giant Cell Formation

The present preclinical and clinical study assessed the inflammatory response to a high-temperature–treated xenogeneic material (Bego-Oss) and the effects of this material on the occurrence of multinucleated giant cells, implantation bed vascularization, and regenerative potential. After evaluation of the material characteristics via scanning electron microscopy, subcutaneous implantation in CD-1 mice was used to assess the inflammatory response to the material for up to 60 days. The clinical aspects of this study involved the use of human bone specimens 6 months after sinus augmentation. Established histologic and histomorphometric analysis methods were applied. After implantation, the material was well integrated into both species without any adverse reactions. Material-induced multinucleated giant cells were observed in both species and were associated with enhanced vascularization. These results revealed the high heat treatment led to an increase in the inflammatory tissue response to the biomaterial, and a combined increase in multinucleated giant cell formation. Further clarification of the differentiation of the multinucleated giant cells toward so-called osteoclast-like cells or foreign-body giant cells is needed to relate these cells to the physicochemical composition of the material.

Giant cell formation: the way to cell death or cell survival?

2011 ◽  
Vol 6 (5) ◽  
pp. 675-684 ◽  
Author(s):  
Rostyslav Horbay ◽  
Rostyslav Stoika
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Giant Cell ◽  
Cell Formation ◽  
Giant Cells ◽  
Cancer Development ◽  
Mitotic Catastrophe ◽  
Giant Cell Formation ◽  
Cycle Disorders

AbstractThe study of giant cells in populations of different tumor cells and evaluation of their role in cancer development is an expanding field. The formation of giant cells has been shown to be followed by mitotic catastrophe, apoptosis, necrosis, and other types of cell elimination. Reports also demonstrate that giant cells can escape cell death and give rise to new cancer cells. However, it is not known if the programmed cell death is involved in this type of cell cycle disorders. Here we describe principal events that are observed during giant cell formation. We also consider the role of giant cells in cancer development, taking into account both published work and our own recent data in this field.

scholarly journals P2X7Receptor and Polykarion Formation

2000 ◽  
Vol 11 (9) ◽  
pp. 3169-3176 ◽  
Author(s):  
Simonetta Falzoni ◽  
Paola Chiozzi ◽  
Davide Ferrari ◽  
Gary Buell ◽  
Francesco Di Virgilio
Keyword(s):  
Cell Fusion ◽  
Cell Formation ◽  
Granulomatous Inflammation ◽  
Giant Cells ◽  
Mononuclear Phagocytes ◽  
Cell Contact ◽  
Giant Cell Formation ◽  
High Level ◽  
Multinucleated Giant Cell Formation

Cell fusion is a central phenomenon during the immune response that leads to formation of large elements called multinucleated giant cells (MGCs) of common occurrence at sites of granulomatous inflammation. We have previously reported on the involvement in this event of a novel receptor expressed to high level by mononuclear phagocytes, the purinergic P2X7receptor. Herein, we show that blockade of this receptor by a specific monoclonal antibody prevents fusion in vitro. In contrast, cell fusion is stimulated by addition of enzymes that destroy extracellular ATP (i.e., apyrase or hexokinase). Experiments performed with phagocytes selected for high (P2X7hyper) or low (P2X7hypo) P2X7expression show that fusion only occurs between P2X7hyper/P2X7hyper and not between P2X7hyper/P2X7hypo or P2X7hypo/P2X7hypo. During MGCs formation we detected activation of caspase 3, an enzyme that is powerfully stimulated by P2X7. Finally, we observed that during MGCs formation, the P2X7receptor is preferentially localized at sites of cell-to-cell contact. These findings support the hypothesis originally put forward by our group that the P2X7receptor participates in multinucleated giant cell formation.

scholarly journals CD301 mediates fusion in IL-4-driven multinucleated giant cell formation

2020 ◽  
Vol 133 (24) ◽  
pp. jcs248864 ◽  
Author(s):  
Patricia J. Brooks ◽  
Yongqiang Wang ◽  
Marco A. Magalhaes ◽  
Michael Glogauer ◽  
Christopher A. McCulloch
Keyword(s):  
Genetic Disorders ◽  
Cell Formation ◽  
Giant Cells ◽  
Lectin Domain ◽  
Raw264.7 Macrophages ◽  
Tandem Mass Tag ◽  
Giant Cell Formation ◽  
Molecular Determinants ◽  
Inflammatory Processes ◽  
And Function

ABSTRACTMultinucleated giant cells (MGCs) are prominent in foreign body granulomas, infectious and inflammatory processes, and auto-immune, neoplastic and genetic disorders, but the molecular determinants that specify the formation and function of these cells are not defined. Here, using tandem mass tag-mass spectrometry, we identified a differentially upregulated protein, C-type lectin domain family 10 member (herein denoted CD301, also known as CLEC10A), that was strongly upregulated in mouse RAW264.7 macrophages and primary murine macrophages undergoing interleukin (IL-4)-induced MGC formation. CD301+ MGCs were identified in biopsy specimens of human inflammatory lesions. Function-inhibiting CD301 antibodies or CRISPR/Cas9 deletion of the two mouse CD301 genes (Mgl1 and Mgl2) inhibited IL-4-induced binding of N-acetylgalactosamine-coated beads by 4-fold and reduced MGC formation by 2.3-fold (P<0.05). IL-4-driven fusion and MGC formation were restored by re-expression of CD301 in the knockout cells. We conclude that in monocytes, IL-4 increases CD301 expression, which mediates intercellular adhesion and fusion processes that are required for the formation of MGCs.This article has an associated First Person interview with the first author of the paper.

scholarly journals Guanylate-Binding Protein-Dependent Noncanonical Inflammasome Activation Prevents Burkholderia thailandensis-Induced Multinucleated Giant Cell Formation

mBio ◽  
2021 ◽  
Author(s):  
Marisa Dilucca ◽  
Saray Ramos ◽  
Kateryna Shkarina ◽  
José Carlos Santos ◽  
Petr Broz
Keyword(s):  
Cell Formation ◽  
Giant Cells ◽  
Innate Immune ◽  
Host Cells ◽  
Inflammasome Activation ◽  
Gram Negative Bacteria ◽  
Giant Cell Formation ◽  
Life Threatening ◽  
Multinucleated Giant Cell Formation ◽  
Guanylate Binding Protein

The Gram-negative bacteria of the Burkholderia species are associated with human diseases ranging from pneumonia to life-threatening melioidosis. Upon infection through inhalation, ingestion, or the percutaneous route, these bacteria can spread and establish granuloma-like lesions resulting from the fusion of host cells to form multinucleated giant cells (MNGCs). Burkholderia resistance to several antibiotics highlights the importance to better understand how the innate immune system controls infections.

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