Direct evidence that inflammatory multinucleate giant cells form by fusion

Murch, Ashleigh; Grounds, Miranda D.; Marshall, Charles A.; Papadimitriou, John

doi:10.1002/path.1711370302

Cited by 98 publications

(32 citation statements)

References 10 publications

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“…HPLC profiles of the liver extracts suggested that 78-98% of the radioactivity present was related to the parent drug. ( 13,21 ). The presence of multinucleated giant cells was the most striking feature of the pathologic changes in the present study.…”

Section: Tissue Distributionsupporting

confidence: 65%

Drug-Induced Hepatic Microgranulomatosis in Cynomolgus Monkeys

et al. 1992

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Section: Tissue Distributionsupporting

confidence: 65%

Drug-Induced Hepatic Microgranulomatosis in Cynomolgus Monkeys

et al. 1992

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“…To date, the basic mechanisms underlying MGC formation are not understood. Previous studies have demonstrated that MGC can be generated in vitro from both monocytes (8) and MAs (9 -11) as a result of cell fusion (12). A number of cell surface adhesion molecules such as CD11a (LFA-1) (13) and ICAM-1 (14), as well as cytokines including IFN-␥, IL-3, IL-4 (15, 16), IL-13 (17), M-CSF, and GM-CSF (10,11), all have been shown to be involved in MGC formation.…”

mentioning

confidence: 99%

Involvement of the Purinergic P2X7 Receptor in the Formation of Multinucleated Giant Cells

Lemaire

Falzoni

Leduc

et al. 2006

The Journal of Immunology

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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. To investigate this, we used HEK 293 cells stably transfected with either 1) the full-length rat P2X7 receptor (P2X7 cells), 2) a rat P2X7 receptor lacking the C-terminal domain (P2X7TC), or 3) a mock vector, and rat alveolar macrophages (MA) expressing the native receptor. P2X7 cells cultured in serum-free medium formed increased numbers of MGC and displayed a higher fusion index compared with mock transfectants. Stimulation of P2X7 pore-forming activity in P2X7 cells by polymyxin B (PMB) further increased significantly the formation of MGC. Conversely, blockers of P2X-receptors including oxidized ATP, brilliant blue G, and pyridoxal phosphate-6-azophenyl-2′-4′-disulfonic acid inhibited significantly MGC formation in both unstimulated and PMB-stimulated P2X7-transfected cells. In contrast, cells transfected with the truncated P2X7TC were devoid of pore-forming activity, did not respond to PMB stimulation, and failed to form enhanced numbers of MGC, thus behaving as mock transfectants. As found for P2X7-transfected cells, PMB also potentiated dose-dependently the formation of multinucleated MA by rat alveolar MA. Pretreatment with oxidized ATP abrogated the PMB stimulatory effects. Together, these data demonstrate unequivocally the participation of P2X7 receptor in the process of MGC formation. Our study also provides evidence suggesting that stimulation of the P2X7 receptor pathway in MA may mediate increased formation of MGC during chronic inflammatory reactions.

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“…33,34) In addition, macrophages form multinucleated foreign-body giant cells, which constitute evidence of a specific inflammatory response evoked by a foreign substance. 35) Two of the six animals in the Ti-implant group showed a moderate inflammatory response. In all animals in the Ti-Zr alloyimplant group, the frequency of cell infiltration into the membrane was smaller than in other implanted groups (Fig.…”

Section: Discussionmentioning

confidence: 93%

Improved Biocompatibility of Titanium–Zirconium (Ti–Zr) Alloy: Tissue Reaction and Sensitization to Ti–Zr Alloy Compared with Pure Ti and Zr in Rat Implantation Study

Ikarashi¹,

Toyoda

Kobayashi

et al. 2005

Mater. Trans.

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Titanium-zirconium (Ti-Zr) binary alloy has better corrosion resistance and mechanical properties than commercially pure Ti. The present study was designed to determine the biocompatibility of Ti-Zr alloy by an implantation test in animal bodies in comparison with pure Ti, Zr, and chromium (Cr) implants as positive controls. Sample specimens were placed in a subcutaneous position in rats for 8 months. No significant decreases in body weight, the weight of any organ, or the weight of any organ relative to body weight were found in the implant groups compared to a no-implant control group. On hematological examination, small differences in several parameters were found in some groups, but these changes were not attributable to the materials implanted. Mitogen-induced blastogenesis was observed in similar degrees among all implant groups. These results suggest that the implantation of test samples did not cause systemic toxicity or a decrease in immune activity. The fibrous capsule membranes around the Ti and Ti-Zr alloy implants were thinner than those around Cr implants. The numbers of macrophages, inflammatory cells, and other cells involved in immune responses in and around the fibrous capsules of the Cr-and Ti-implant groups were higher than those of the Ti-Zr alloy-and Zr-implant groups. The Ti-Zr alloy had the lowest total score of tissue responses among the materials tested. None of the animals from the Ti-, Zr-, and Ti-Zr alloy-implant groups exhibited a skin reaction following exposure to Ti or Zr salt solutions. These results indicate the Ti-Zr alloy has better biocompatibility than Ti for use as an artificial surgical implant.

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Direct evidence that inflammatory multinucleate giant cells form by fusion

Cited by 98 publications

References 10 publications

Drug-Induced Hepatic Microgranulomatosis in Cynomolgus Monkeys

Drug-Induced Hepatic Microgranulomatosis in Cynomolgus Monkeys

Involvement of the Purinergic P2X7 Receptor in the Formation of Multinucleated Giant Cells

Improved Biocompatibility of Titanium–Zirconium (Ti–Zr) Alloy: Tissue Reaction and Sensitization to Ti–Zr Alloy Compared with Pure Ti and Zr in Rat Implantation Study

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Direct evidence that inflammatory multinucleate giant cells form by fusion

Cited by 98 publications

References 10 publications

Drug-Induced Hepatic Microgranulomatosis in Cynomolgus Monkeys

Drug-Induced Hepatic Microgranulomatosis in Cynomolgus Monkeys

Involvement of the Purinergic P2X7 Receptor in the Formation of Multinucleated Giant Cells

Improved Biocompatibility of Titanium&ndash;Zirconium (Ti&ndash;Zr) Alloy: Tissue Reaction and Sensitization to Ti&ndash;Zr Alloy Compared with Pure Ti and Zr in Rat Implantation Study

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Improved Biocompatibility of Titanium–Zirconium (Ti–Zr) Alloy: Tissue Reaction and Sensitization to Ti–Zr Alloy Compared with Pure Ti and Zr in Rat Implantation Study