giant cells

Summary

Summary: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus.

Top Publications

  1. Siddique S, Wieczorek K, Szakasits D, Kreil D, Bohlmann H. The promoter of a plant defensin gene directs specific expression in nematode-induced syncytia in Arabidopsis roots. Plant Physiol Biochem. 2011;49:1100-7 pubmed publisher
    ..These results were supported by the analysis of promoter::GUS lines. After infection with H. schachtii all GUS lines showed a strong staining in syncytia at 5 and 15 dpi. This expression pattern was confirmed by in situ RT-PCR...
  2. Delpeut S, Rudd P, Labonte P, von Messling V. Membrane fusion-mediated autophagy induction enhances morbillivirus cell-to-cell spread. J Virol. 2012;86:8527-35 pubmed publisher
  3. Jaouannet M, Perfus Barbeoch L, Deleury E, Magliano M, Engler G, Vieira P, et al. A root-knot nematode-secreted protein is injected into giant cells and targeted to the nuclei. New Phytol. 2012;194:924-31 pubmed publisher
    ..The protein Mi-EFF1 injected within the feeding cells is targeted at the nuclei where it may manipulate nuclear functions of the host cell...
  4. Park J, Rosen A, Saffitz J, Asimaki A, Litovsky S, Mackey Bojack S, et al. Expression of cathepsin K and tartrate-resistant acid phosphatase is not confined to osteoclasts but is a general feature of multinucleated giant cells: systematic analysis. Rheumatology (Oxford). 2013;52:1529-33 pubmed publisher
    Cathepsin K and tartrate-resistant acid phosphatase (TRAP) are two proteins expressed in osteoclastic giant cells. Recently we showed that lesional multinucleated giant cells (MNGs) in pulmonary granulomatosis with polyangiitis expressed ..
  5. Matsuyama S, Nagata N, Shirato K, Kawase M, Takeda M, Taguchi F. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J Virol. 2010;84:12658-64 pubmed publisher
    ..Our findings suggest that the TMPRSS2 expressed in lung tissues may be a determinant of viral tropism and pathogenicity at the initial site of SARS-CoV infection...
  6. Erbar S, Maisner A. Nipah virus infection and glycoprotein targeting in endothelial cells. Virol J. 2010;7:305 pubmed publisher
    ..However, the prerequisites for correct protein targeting differ markedly in the two polarized cell types...
  7. Chen Y, Allars M, Maiti K, Angeli G, Abou Seif C, Smith R, et al. Factors affecting cytotrophoblast cell viability and differentiation: Evidence of a link between syncytialisation and apoptosis. Int J Biochem Cell Biol. 2011;43:821-8 pubmed publisher
  8. Prokop S, Heppner F, Goebel H, Stenzel W. M2 polarized macrophages and giant cells contribute to myofibrosis in neuromuscular sarcoidosis. Am J Pathol. 2011;178:1279-86 pubmed publisher
    ..Monocytes/macrophages and giant cells in granulomas of muscle tissue from patients with sarcoidosis show a status of alternative activation (M2) ..
  9. Maksymov V, Khalifa M, Bussey A, Carter B, Hogan M. Undifferentiated (anaplastic) carcinoma of the pancreas with osteoclast-like giant cells showing various degree of pancreas duct involvement. A case report and literature review. JOP. 2011;12:170-6 pubmed
    Undifferentiated (anaplastic) carcinoma of the pancreas with osteoclast-like giant cells is exceedingly rare...

More Information

Publications62

  1. Holt D, Grainger D. Multinucleated giant cells from fibroblast cultures. Biomaterials. 2011;32:3977-87 pubmed publisher
    Many multinucleated giant cells are well-known to form from macrophage origin. Those formed from other cell types are less described, but may be as prevalent in pathological tissue...
  2. McNally A, Anderson J. Macrophage fusion and multinucleated giant cells of inflammation. Adv Exp Med Biol. 2011;713:97-111 pubmed publisher
    Macrophages undergo fusion with other macrophages to form the hallmark multinucleated giant cells of chronic inflammation...
  3. Conejero L, Patel N, de Reynal M, Oberdorf S, Prior J, Felgner P, et al. Low-dose exposure of C57BL/6 mice to burkholderia pseudomallei mimics chronic human melioidosis. Am J Pathol. 2011;179:270-80 pubmed publisher
    ..in humans, such as development of a collagen cord that encapsulates the lesions, the presence of multinucleated giant cells, and granulomas with a caseous necrotic center, which may explain why chronic melioidosis is often misdiagnosed ..
  4. Stanek J, Biesiada J. Sensitivity and specificity of finding of multinucleate trophoblastic giant cells in decidua in placentas from high-risk pregnancies. Hum Pathol. 2012;43:261-8 pubmed publisher
    ..analysis of sensitivity and specificity of clustered placental basal plate multinucleate trophoblastic giant cells for various clinical conditions and placental lesions associated with fetal and placental hypoxia...
  5. Angeletti S, Sanchez J, Chamley L, Genti Raimondi S, Perillo M. StarD7 behaves as a fusogenic protein in model and cell membrane bilayers. Biochim Biophys Acta. 2012;1818:425-33 pubmed publisher
    ..Moreover, this process was favored by phosphatidylethanolamine which is known to stabilize non-lamellar phases considered as intermediary in the fusion process. Altogether these findings allow postulate StarD7 as a fusogenic protein...
  6. Hoque S, Ohtsuki T, Tatsumi M, Shimizu N, Islam S, Jinno Oue A, et al. Lack of the trans-receptor mechanism of HIV-1 infection: CD4- and coreceptor-independent incorporation of HIV-1-resistant cells into syncytia induced by HIV-1. Microbes Infect. 2012;14:357-68 pubmed publisher
    ..Our study demonstrates that HIV-1-resistant cells can be incorporated into syncytia induced by HIV-1 and this incorporation may partially be mediated through adhesion molecules...
  7. Villenave R, Thavagnanam S, Sarlang S, Parker J, Douglas I, Skibinski G, et al. In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo. Proc Natl Acad Sci U S A. 2012;109:5040-5 pubmed publisher
    ..As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics...
  8. Kim S, Xiao S, Shive H, Collins P, Samal S. Replication, neurotropism, and pathogenicity of avian paramyxovirus serotypes 1-9 in chickens and ducks. PLoS ONE. 2012;7:e34927 pubmed publisher
    ..The link between the presence of a furin cleavage site in the F protein, syncytium formation, systemic spread, and virulence that has been well-established with APMV-1 pathotypes was not evident with the other APMV serotypes...
  9. Siddique S, Sobczak M, Tenhaken R, Grundler F, Bohlmann H. Cell wall ingrowths in nematode induced syncytia require UGD2 and UGD3. PLoS ONE. 2012;7:e41515 pubmed publisher
    ..schachtii resulting in smaller syncytia, lower number of developing nematodes, and smaller females...
  10. F rir G, H nchen A, Fran ois K, Hoorelbeke B, Huskens D, Dettner F, et al. Feglymycin, a unique natural bacterial antibiotic peptide, inhibits HIV entry by targeting the viral envelope protein gp120. Virology. 2012;433:308-19 pubmed publisher
    ..In conclusion, FGM is a unique prototype lead peptide with potential for further development of more potent anti-HIV derivatives...
  11. Mould A, Morgan M, Li L, Bikoff E, Robertson E. Blimp1/Prdm1 governs terminal differentiation of endovascular trophoblast giant cells and defines multipotent progenitors in the developing placenta. Genes Dev. 2012;26:2063-74 pubmed publisher
    ..Loss of function disrupts specification of the invasive spiral artery-associated trophoblast giant cells (SpA-TGCs) surrounding maternal blood vessels and severely compromises the ability of the spongiotrophoblast ..
  12. Curtis R, Pankaj -, Powers S, Napier J, Matthes M. The Arabidopsis F-box/Kelch-repeat protein At2g44130 is upregulated in giant cells and promotes nematode susceptibility. Mol Plant Microbe Interact. 2013;26:36-43 pubmed publisher
  13. Binder F, Hayakawa M, Choo M, Sano Y, Park J. Interleukin-4-induced ?-catenin regulates the conversion of macrophages to multinucleated giant cells. Mol Immunol. 2013;54:157-63 pubmed publisher
    ..IL-4 also induces macrophages to fuse together and form multinucleated giant cells (MGCs)...
  14. Corbel C, Diabangouaya P, Gendrel A, Chow J, Heard E. Unusual chromatin status and organization of the inactive X chromosome in murine trophoblast giant cells. Development. 2013;140:861-72 pubmed publisher
    ..most lineages, with significant levels of escape from XCI mainly in one extra-embryonic cell type: trophoblast giant cells (TGCs)...
  15. Won K, Kalil R, Kim Y, Park Y. RANK signalling in bone lesions with osteoclast-like giant cells. Pathology. 2011;43:318-21 pubmed publisher
    ..Giant cell tumours, chondroblastomas, and aneurysmal bone cysts harbour osteolytic lesions containing osteoclast-like giant cells. We investigated the characteristics of the RANKL signalling pathway in each of these bone lesions.
  16. Subbiah M, Khattar S, Collins P, Samal S. Mutations in the fusion protein cleavage site of avian paramyxovirus serotype 2 increase cleavability and syncytium formation but do not increase viral virulence in chickens. J Virol. 2011;85:5394-405 pubmed publisher
    ..Furthermore, cleavage of the F protein is not a determinant of APMV-2 pathogenicity in chickens...
  17. Bergmann F, Esposito I, Michalski C, Herpel E, Friess H, Schirmacher P. Early undifferentiated pancreatic carcinoma with osteoclastlike giant cells: direct evidence for ductal evolution. Am J Surg Pathol. 2007;31:1919-25 pubmed
    ..To a variable degree, they may contain osteoclastlike giant cells and are then sometimes referred to as osteoclastlike giant cell tumors...
  18. Guilbert L, Riddell M, Winkler Lowen B. Caspase activation is not required for villous cytotrophoblast fusion into syncytiotrophoblasts. Placenta. 2010;31:982-8 pubmed publisher
    ..We conclude that activation of caspases in general, and caspase-8 in particular, is not required for villous CT differentiation into ST. However, another role of intact caspase-8 (proform) in CT differentiation remains possible...
  19. Aplin J. Developmental cell biology of human villous trophoblast: current research problems. Int J Dev Biol. 2010;54:323-9 pubmed publisher
    ..Maternally delivered insulin-like growth factors stimulate growth and might be therapeutically useful when endogenous growth pathways falter...
  20. Gordón Alonso M, Yanez Mo M, Barreiro O, Alvarez S, Munoz Fernandez M, Valenzuela Fernandez A, et al. Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion. J Immunol. 2006;177:5129-37 pubmed
    ..Accordingly, overexpression of CD81 and CD9 rendered cells less susceptible to Env-mediated syncytia formation. These data indicate that CD9 and CD81 have an important role in membrane fusion induced by HIV-1 envelope...
  21. Helming L, Gordon S. Macrophage fusion induced by IL-4 alternative activation is a multistage process involving multiple target molecules. Eur J Immunol. 2007;37:33-42 pubmed
    Multinucleated giant cells, characteristic of granulomatous infections, originate from fusion of macrophages, however, little is known about the underlying mechanism...
  22. Simmons D, Fortier A, Cross J. Diverse subtypes and developmental origins of trophoblast giant cells in the mouse placenta. Dev Biol. 2007;304:567-78 pubmed
    Trophoblast giant cells (TGCs) are the first terminally differentiated subtype to form in the trophoblast cell lineage in rodents...
  23. Ullah Z, Kohn M, Yagi R, Vassilev L, DePamphilis M. Differentiation of trophoblast stem cells into giant cells is triggered by p57/Kip2 inhibition of CDK1 activity. Genes Dev. 2008;22:3024-36 pubmed publisher
    ..Expression of p57 in TG cells was restricted to G-phase nuclei to allow CDK activation of S phase. Thus, endoreduplication in TS cells is triggered by p57 inhibition of CDK1 with concomitant suppression of the DNA damage response by p21...
  24. Hirano H, Morita K, Tachibana S, Okimura A, Fujisawa T, Ouchi S, et al. Undifferentiated carcinoma with osteoclast-like giant cells arising in a mucinous cystic neoplasm of the pancreas. Pathol Int. 2008;58:383-9 pubmed publisher
    ..Osteoclast-like giant cells (OGC) were also contained in the sarcomatous component...
  25. Hu D, Cross J. Development and function of trophoblast giant cells in the rodent placenta. Int J Dev Biol. 2010;54:341-54 pubmed publisher
    Trophoblast giant cells (TGCs) are the first cell type to terminally differentiate during embryogenesis and are of vital importance for implantation and modulation of post-implantation placentation...
  26. Watanabe K, Shin E, Hashino M, Tachibana M, Watarai M. Toll-like receptor 2 and class B scavenger receptor type I are required for bacterial uptake by trophoblast giant cells. Mol Immunol. 2010;47:1989-96 pubmed publisher
    ..These results suggested that the phagocytic activity of TG cells is mediated by both TLR2 and SR-BI...
  27. Reichelt M, Zerboni L, Arvin A. Mechanisms of varicella-zoster virus neuropathogenesis in human dorsal root ganglia. J Virol. 2008;82:3971-83 pubmed publisher
    ..These mechanisms of VZV neuropathogenesis help to account for the often severe neurologic consequences of herpes zoster...
  28. Lemaire I, Falzoni S, Leduc N, Zhang B, Pellegatti P, Adinolfi E, et al. Involvement of the purinergic P2X7 receptor in the formation of multinucleated giant cells. J Immunol. 2006;177:7257-65 pubmed
    Multinucleated giant cells (MGC), a hallmark of chronic inflammatory reactions, remain an enigma of cell biology. There is evidence implicating the purinergic P2X7 receptor in the fusion process leading to MGC...
  29. Gattegno T, Mittal A, Valansi C, Nguyen K, Hall D, Chernomordik L, et al. Genetic control of fusion pore expansion in the epidermis of Caenorhabditis elegans. Mol Biol Cell. 2007;18:1153-66 pubmed
    ..The first cell fusion does not trigger a wave of orderly fusions in either direction. Ultrastructural studies show that epidermal syncytiogenesis require eff-1 activities to initiate and expand membrane merger...
  30. Komatsu D, Abe T, Sano Y, Shimazaki K, Tomita M, Kanayama N, et al. Increase of the trophoblast giant cells with prolactin-releasing peptide (PrRP) receptor expression in p53-null mice. Mol Reprod Dev. 2007;74:1089-94 pubmed
    Trophoblast giant cells in the mouse placentas are polyploid cells that form as a result of endoreduplication...
  31. Murphy S, Gaulton G. TR1.3 viral pathogenesis and syncytium formation are linked to Env-Gag cooperation. J Virol. 2007;81:10777-85 pubmed
    ..3 and W102G viruses. Collectively, these data suggest that the TR1.3 and W102G viruses induce cell fusion by the fusion-from-without pathway...
  32. Zhu X, Price N, Gilman R, Recarvarren S, Friedland J. Multinucleate giant cells release functionally unopposed matrix metalloproteinase-9 in vitro and in vivo. J Infect Dis. 2007;196:1076-9 pubmed
    Multinucleated giant cells (MGCs) are characteristic of granulomatous inflammation. Matrix metalloproteinase (MMP)-9, the major monocyte-derived matrix metalloproteinase, is key in inflammatory tissue damage...
  33. Wieczorek K, Hofmann J, Blöchl A, Szakasits D, Bohlmann H, Grundler F. Arabidopsis endo-1,4-beta-glucanases are involved in the formation of root syncytia induced by Heterodera schachtii. Plant J. 2008;53:336-51 pubmed
    ..A distinctly reduced number of females developed in cel2 and kor3 T-DNA mutants, and we therefore conclude that endo-1,4-beta-glucanases play an important role in the formation and function of syncytia...
  34. Vaideeswar P, George S, Kane S, Chaturvedi R, Pandit S. Extranodal follicular dendritic cell sarcoma of the tonsil - case report of an epithelioid cell variant with osteoclastic giant cells. Pathol Res Pract. 2009;205:149-53 pubmed publisher
    ..tumor in a 50-year-old man, which was composed exclusively of large polygonal cells and numerous osteoclastic giant cells that resembled a giant cell carcinoma...
  35. Barcala M, Garcia A, Cabrera J, Casson S, Lindsey K, Favery B, et al. Early transcriptomic events in microdissected Arabidopsis nematode-induced giant cells. Plant J. 2010;61:698-712 pubmed publisher
    Root-knot nematodes differentiate highly specialized feeding cells in roots (giant cells, GCs), through poorly characterized mechanisms that include extensive transcriptional changes...
  36. Klink V, Hosseini P, Matsye P, Alkharouf N, Matthews B. A gene expression analysis of syncytia laser microdissected from the roots of the Glycine max (soybean) genotype PI 548402 (Peking) undergoing a resistant reaction after infection by Heterodera glycines (soybean cyst nematode). Plant Mol Biol. 2009;71:525-67 pubmed publisher
    ..max genotype, Peking...
  37. Szakasits D, Heinen P, Wieczorek K, Hofmann J, Wagner F, Kreil D, et al. The transcriptome of syncytia induced by the cyst nematode Heterodera schachtii in Arabidopsis roots. Plant J. 2009;57:771-84 pubmed publisher
    ..This analysis revealed that syncytia are transcriptionally clearly different from roots (and all other organs), as well as from other root tissues...
  38. Day R, Herridge R, Ambrose B, Macknight R. Transcriptome analysis of proliferating Arabidopsis endosperm reveals biological implications for the control of syncytial division, cytokinin signaling, and gene expression regulation. Plant Physiol. 2008;148:1964-84 pubmed publisher
    ..In summary, the data generated provide a useful resource providing novel insight into early seed development and identify new target genes for further characterization...
  39. Siddique S, Endres S, Atkins J, Szakasits D, Wieczorek K, Hofmann J, et al. Myo-inositol oxygenase genes are involved in the development of syncytia induced by Heterodera schachtii in Arabidopsis roots. New Phytol. 2009;184:457-72 pubmed publisher
    ..Furthermore, syncytia in double mutants were significantly smaller than in wild-type plants. * Our data demonstrate an important role of the MIOX genes for syncytium development and for the development of female nematodes...
  40. Papalas J, Balmer N, Wallace C, Sangueza O. Ossifying dermatofibroma with osteoclast-like giant cells: report of a case and literature review. Am J Dermatopathol. 2009;31:379-83 pubmed publisher
    ..Ossifying dermatofibroma with osteoclast-like giant cells is an uncommon variant that has only rarely been reported...
  41. Fendrick S, Xue Q, Streit W. Formation of multinucleated giant cells and microglial degeneration in rats expressing a mutant Cu/Zn superoxide dismutase gene. J Neuroinflammation. 2007;4:9 pubmed
    ..The purpose of this study was to provide a histopathological evaluation of the microglial neuroinflammatory response in a rodent model of ALS, the SOD1G93A transgenic rat...
  42. Watanabe K, Tachibana M, Kim S, Watarai M. Participation of ezrin in bacterial uptake by trophoblast giant cells. Reprod Biol Endocrinol. 2009;7:95 pubmed publisher
    ..However, the mechanism of bacterial uptake by TG cells is not completely understood. Here we identified ezrin, a member of ezrin-radixin-moesin (ERM) protein family, as a molecule associated with Hsc70...
  43. Hofmann J, Wieczorek K, Blöchl A, Grundler F. Sucrose supply to nematode-induced syncytia depends on the apoplasmic and symplasmic pathways. J Exp Bot. 2007;58:1591-601 pubmed
  44. Kadiu I, Ricardo Dukelow M, Ciborowski P, Gendelman H. Cytoskeletal protein transformation in HIV-1-infected macrophage giant cells. J Immunol. 2007;178:6404-15 pubmed
    ..Such events favor the virus over the host cell and provide insights into macrophage defense mechanisms used to contain viral growth and how they may be affected during progressive HIV-1 infection...
  45. Yamaguchi T, Takahashi H, Kagawa R, Takeda R, Sakata S, Yamamoto M, et al. Huge pseudocyst of the pancreas caused by poorly differentiated invasive ductal adenocarcinoma with osteoclast-like giant cells: report of a case. Hepatogastroenterology. 2007;54:599-601 pubmed
    ..was histologically proven to be poorly differentiated ductal adenocarcinoma in combination with osteoclast-like giant cells. The pseudocyst was considered to be due to the stenosis of the main pancreatic duct caused by carcinoma of the ..
  46. Chopra S, Wu M, Imagawa D, Lee J, Gu M. Endoscopic ultrasound-guided fine-needle aspiration of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: a report of 2 cases with literature review. Diagn Cytopathol. 2007;35:601-6 pubmed
    Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas is rare. Histologically it mimics the giant cell tumor of the bone and may be associated with a ductal adenocarcinoma...
  47. Moreno J, Mikhailenko I, TONDRAVI M, Keegan A. IL-4 promotes the formation of multinucleated giant cells from macrophage precursors by a STAT6-dependent, homotypic mechanism: contribution of E-cadherin. J Leukoc Biol. 2007;82:1542-53 pubmed
    Multinucleated giant cells (MNG) are central players in the inflammatory response to foreign materials and in adverse responses to implants...
  48. Terasaki F, Fujita M, Shimomura H, Tsukada B, Otsuka K, Otsuka K, et al. Enhanced expression of myeloid-related protein complex (MRP8/14) in macrophages and multinucleated giant cells in granulomas of patients with active cardiac sarcoidosis. Circ J. 2007;71:1545-50 pubmed
    ..The expression of MRP8/14 in patients with cardiac sarcoidosis and idiopathic dilated cardiomyopathy (DCM) was investigated...
  49. Gonzalo P, Guadamillas M, Hernández Riquer M, Pollán A, Grande García A, Bartolomé R, et al. MT1-MMP is required for myeloid cell fusion via regulation of Rac1 signaling. Dev Cell. 2010;18:77-89 pubmed publisher
  50. Mustafa T, Wiker H, Mørkve O, Sviland L. Differential expression of mycobacterial antigen MPT64, apoptosis and inflammatory markers in multinucleated giant cells and epithelioid cells in granulomas caused by Mycobacterium tuberculosis. Virchows Arch. 2008;452:449-56 pubmed publisher
    ..The aim of this study was to compare the epithelioid cells (ECs) and multinucleated giant cells (MGCs) in the granulomas caused by Mycobacterium tuberculosis complex organisms...
  51. Guedan S, Gros A, Cascallo M, Vile R, Mercade E, Alemany R. Syncytia formation affects the yield and cytotoxicity of an adenovirus expressing a fusogenic glycoprotein at a late stage of replication. Gene Ther. 2008;15:1240-5 pubmed publisher
    ..In contrast, at low MOI, infected cells formed syncytia where only one nucleus contained virus DNA, decreasing total virus production but increasing cytotoxicity...
  52. Wheatley D. Growing evidence of the repopulation of regressed tumours by the division of giant cells. Cell Biol Int. 2008;32:1029-30 pubmed publisher
  53. Richard J, Leikina E, Chernomordik L. Cytoskeleton reorganization in influenza hemagglutinin-initiated syncytium formation. Biochim Biophys Acta. 2009;1788:450-7 pubmed publisher
    ..Effective syncytium formation for cells with disorganized actin and microtubule cytoskeleton argues against hypothesis that cytoskeleton drives fusion expansion...