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

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.

Author(s):  
Jacob L. Stockton ◽  
Alfredo G. Torres

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.


2020 ◽  
Vol 8 (11) ◽  
pp. 1637
Author(s):  
Jacob L. Stockton ◽  
Alfredo G. Torres

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.


Author(s):  
Samar Khan

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.


PEDIATRICS ◽  
1958 ◽  
Vol 21 (3) ◽  
pp. 436-442
Author(s):  
C. Lenore Simpson ◽  
Donald Pinkel

A fatal case of measles complicating leukemia in an infant is reported. Giant-cell pneumonia and a few giant cells in lymph nodes were seen as in previously reported cases. In addition, necroses in liver, lymph nodes, thymus, pancreas and kidney associated with giant-cell formation and inclusion bodies were observed.


Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1369-1374 ◽  
Author(s):  
J Oval ◽  
OW Jones ◽  
M Montoya ◽  
R Taetle

A strictly factor-dependent cell line (UCSD/AML1) was established from a patient with the syndrome of multilineage acute leukemia with high platelets. The patient's cells and the cell line karyotype were 45,XX,- 7,t(3;3)(q21;q26), typical of the syndrome of acute leukemia with high platelets. The cell line expresses CD34, CD7, TdT, and myeloid (CD13, CD14, CD33) and megakaryocyte/platelet (CD36, CD41, CD42b, CDw49b) antigens. In short-term culture, UCSD/AML1 cells proliferate in response to interleukin-3 (IL-3), IL-4, IL-6, macrophage colony- stimulating factor (M-CSF), and granulocyte-macrophage CSF (GM-CSF), but not IL-1, IL-2, IL-5, or G-CSF. In long-term culture, proliferation can be sustained by GM-CSF, IL-6, or M-CSF. When maintained in GM-CSF, a small percentage of cells form multinucleated megakaryocyte-like giant cells. Culture with GM-CSF combined with IL-6, but not with IL-6 alone, increased giant cell formation fourfold to sevenfold. IL-6 alone or in combination with GM-CSF increased expression of platelet-related antigens. In contrast, culture with phorbol ester induced formation of macrophage-like cells. UCSD/AML1 is the first human acute nonlymphocytic leukemia cell line established from a patient with an acute leukemia syndrome associated with a specific chromosome abnormality.


1976 ◽  
Vol 22 (3) ◽  
pp. 431-434 ◽  
Author(s):  
K. G. Johnson ◽  
I. J. Mcdonald

Growth of Neisseria perflava, Neisseria cinerea, and Neisseria sicca strain Kirkland in media supplemented with sucrose (0.5 to 5.0% w/v) resulted in the formation of giant cells. Response to sucrose was specific in that a variety of other carbohydrates did not mediate giant cell formation. Giant cells appeared only under growth conditions and did not lyse upon transfer to medium lacking sucrose or upon resuspension in hypotonic media. Reversion of giant to normal cells occurred when giant cells were used as inocula and allowed to multiply in media lacking sucrose.


2015 ◽  
Vol 41 (5) ◽  
pp. e212-e222 ◽  
Author(s):  
Mike Barbeck ◽  
Samuel Udeabor ◽  
Jonas Lorenz ◽  
Markus Schlee ◽  
Marzellus Grosse Holthaus ◽  
...  

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.


2009 ◽  
Vol 16 (1) ◽  
pp. 53-57 ◽  
Author(s):  
William G Brodbeck ◽  
James M Anderson

1958 ◽  
Vol 32 (3) ◽  
pp. 135-144 ◽  
Author(s):  
C. S. Cole ◽  
H. W. Howard

Giant cell formation was studied in the roots of potatoes grown in a soil infested with Heterodera rostochiensis.Some indication of giant cell formation was found in roots fixed 14 days after planting of sprouted tubers in the infested soil.Giant cells may be formed by the cells of the cortex, the endodermis, the pericycle and the parenchyma cells of the central vascular strand.The first giant cells appear to be formed in the cortex and pericycle.Giant cells in the cortex are only found near the head of an eelworm.Giant cell formation by the parenchyma cells of the central vascular strand leads to no cambium and hence no secondary xylem being produced in those sectors of the root where they occur.The occurrence of sectors of the root in which there is no secondary xylem gives the central vascular strand an irregular appearance.Some giant cells may be multinucleate. They all have granular cytoplasm.


1999 ◽  
Vol 2 (4) ◽  
pp. 353-359 ◽  
Author(s):  
George Koukoulis ◽  
Giorgina Mieli-Vergani ◽  
Bernard Portmann

The mechanism of liver giant cell formation is not clarified. Some authors consider the giant cells regenerative, others, degenerative. Paraffin sections of 10 archival cases of idiopathic neonatal hepatitis (INH), 8 of extrahepatic biliary atresia (EHBA), and 5 normal liver samples were immunostained with two well-characterized cell proliferation markers: anti-PCNA monoclonal antibody (MAb) (clone PC-10) and MAb MIB-1, which detects Ki-67, a nuclear proliferation-related antigen. In addition, polyclonal antibody to carcinoembryonic antigen (CEA) was used to identify remnants of canalicular, therefore hepatocytic, membranes in giant cells. Quantitative analysis of immunostaining was done by estimating PCNA and Ki-67 indices separately in giant cells and in nongiant hepatocytes. In normal samples, mean PCNA and Ki-67 indices were 1.22% and 0.74%, respectively. In the cases of INH and EHBA, only a small minority of giant cells showed PCNA or Ki-67 staining limited to occasional peripherally located nuclei. PCNA and Ki-67 indices were significantly higher in the non–giant cell compartment. CEA staining was seen only in rare giant cells as centrally located canalicular remnants bordered by polarized nuclei, suggesting that they had been formed from rosettes through dissolution of cell membranes. Other giant cells shared CEA-labeled canalicular membranes with mononuclear hepatocytes in rosettes. These findings indicate that the giant cells in INH and EHBA are not regenerative cells, they are not formed by amitotic division of nuclei in syncytia, and that fusion of rosette-forming hepatocytes is a possible mechanism of their formation.


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