Role of NADPH Oxidase in Formation and Function of Multinucleated Giant Cells

AbstractCell membrane fusion and multinucleation in macrophages are associated with physiologic homeostasis as well as disease. Osteoclasts are multinucleated macrophages that resorb bone through increased metabolic activity resulting from cell fusion. Fusion of macrophages also generates multinucleated giant cells (MGCs) in white adipose tissue (WAT) of obese individuals. For years, our knowledge of MGCs in WAT has been limited to their description as part of crown-like structures (CLS) surrounding damaged adipocytes. However, recent evidence indicates that these cells can phagocytose oversized lipid remnants, suggesting that, as in osteoclasts, cell fusion and multinucleation are required for specialized catabolic functions. We thus reason that WAT MGCs can be viewed as functionally analogous to osteoclasts and refer to them in this article as adipoclasts. We first review current knowledge on adipoclasts and their described functions. In view of recent advances in single cell genomics, we describe WAT macrophages from a ‘fusion perspective’ and speculate on the ontogeny of adipoclasts. Specifically, we highlight the role of CD9 and TREM2, two plasma membrane markers of lipid-associated macrophages in WAT, which have been previously described as regulators of fusion and multinucleation in osteoclasts and MGCs. Finally, we consider whether strategies aiming to target WAT macrophages can be more selectively directed against adipoclasts.

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An Overview of the Derivation and Function of Multinucleated Giant Cells and Their Role in Pathologic Processes

American Journal Of Pathology ◽

10.1016/j.ajpath.2019.02.006 ◽

2019 ◽

Vol 189 (6) ◽

pp. 1145-1158 ◽

Cited By ~ 17

Author(s):

Patricia J. Brooks ◽

Michael Glogauer ◽

Christopher A. McCulloch

Keyword(s):

Giant Cells ◽

Multinucleated Giant Cells ◽

And Function ◽

Pathologic Processes

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Role of Fine Needle Aspiration in the Diagnosis of the Rare Disease of Langerhans Cell Histiocytosis in a Child

Case Reports in Pathology ◽

10.1155/2014/724895 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3

Author(s):

Seema Lale ◽

Daniel Soto ◽

Patricia G. Wasserman

Keyword(s):

Langerhans Cell Histiocytosis ◽

Parasitic Infection ◽

Giant Cells ◽

Needle Aspiration ◽

Kimura’S Disease ◽

Cat Scratch Disease ◽

Multinucleated Giant Cells ◽

Dermatopathic Lymphadenitis ◽

Massive Lymphadenopathy

Langerhan’s cell histiocytosis (LCH) results from the proliferation of immunophenotypically and functionally immature, morphologically rounded Langerhan’s cells along with eosinophils, macrophages, lymphocytes, and, commonly, multinucleated giant cells. Here we report a case in a 6-year-old boy of differential diagnoses including dermatopathic lymphadenitis (DL), parasitic infection, Kimura’s disease, hypersensitivity reactions, cat-scratch disease, sinus histiocytosis with massive lymphadenopathy (SHML), hyperplasic lymph nodes, and lymphoma.

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Multinucleated Giant Cell Formation as a Portal to Chronic Bacterial Infections

10.20944/preprints202009.0471.v1 ◽

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.

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Multinucleated Giant Cell Formation as a Portal to Chronic Bacterial Infections

Microorganisms ◽

10.3390/microorganisms8111637 ◽

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.

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Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts

Molecular Biology of the Cell ◽

10.1091/mbc.e13-07-0363 ◽

2014 ◽

Vol 25 (3) ◽

pp. 380-396 ◽

Cited By ~ 29

Author(s):

Dan Georgess ◽

Marlène Mazzorana ◽

José Terrado ◽

Christine Delprat ◽

Christophe Chamot ◽

...

Keyword(s):

Bone Resorption ◽

Giant Cells ◽

Actin Dynamics ◽

Multinucleated Giant Cells ◽

Resorption Lacuna ◽

Actin Turnover ◽

Bona Fide ◽

Mineral Matrix ◽

Monocytic Lineage

The function of osteoclasts (OCs), multinucleated giant cells (MGCs) of the monocytic lineage, is bone resorption. To resorb bone, OCs form podosomes. These are actin-rich adhesive structures that pattern into rings that drive OC migration and into “sealing-zones” (SZs) that confine the resorption lacuna. Although changes in actin dynamics during podosome patterning have been documented, the mechanisms that regulate these changes are largely unknown. From human monocytic precursors, we differentiated MGCs that express OC degradation enzymes but are unable to resorb the mineral matrix. We demonstrated that, despite exhibiting bona fide podosomes, these cells presented dysfunctional SZs. We then performed two-step differential transcriptomic profiling of bone-resorbing OCs versus nonresorbing MGCs to generate a list of genes implicated in bone resorption. From this list of candidate genes, we investigated the role of Rho/Rnd3. Using primary RhoE-deficient OCs, we demonstrated that RhoE is indispensable for OC migration and bone resorption by maintaining fast actin turnover in podosomes. We further showed that RhoE activates podosome component cofilin by inhibiting its Rock-mediated phosphorylation. We conclude that the RhoE-Rock-cofilin pathway, by promoting podosome dynamics and patterning, is central for OC migration, SZ formation, and, ultimately, bone resorption.

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Scanning electron microscopic study of collagen fibrillogenesis and extracellular compartmentalization in the chick embryo tendon

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142669 ◽

1986 ◽

Vol 44 ◽

pp. 208-209

Author(s):

Grace C.H. Yang

Keyword(s):

Chick Embryo ◽

Extracellular Space ◽

Fibroblast Cell ◽

Collagen Fibrils ◽

Electron Microscopic ◽

Voltage Electron ◽

Scanning Electron Microscopic Study ◽

Microscopic Studies ◽

And Function

The size and organization of collagen fibrils in the extracellular matrix is an important determinant of tissue structure and function. The synthesis and deposition of collagen involves multiple steps which begin within the cell and continue in the extracellular space. High-voltage electron microscopic studies of the chick embryo cornea and tendon suggested that the extracellular space is compartmentalized by the fibroblasts for the regulation of collagen fibril, bundle, and tissue specific macroaggregate formation. The purpose of this study is to gather direct evidence regarding the association of the fibroblast cell surface with newly formed collagen fibrils, and to define the role of the fibroblast in the control and the precise positioning of collagen fibrils, bundles, and macroaggregates during chick tendon development.

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