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Updated: Aug 11, 2026

Development and Identification of a Novel Subpopulation of Human Neutrophil-derived Giant Phagocytes In Vitro
Published on: January 25, 2017
Inflammatory cytokine production by immunological and foreign body multinucleated giant cells
R Hernandez-Pando1, Q L Bornstein, D Aguilar Leon
1Experimental Pathology Laboratory, Department of Pathology, Instituto Nacional de la Nutricion 'Salvador Zubiran', Mexico City, Mexico.
Abstract:
Multinucleated giant cells (MGC) are a common feature of granulomas. The mechanism of their formation has been studied extensively, but their function has not been completely characterized. A new method for the in vivo production of MGC was developed involving subcutaneous injection of microscopic nitrocellulose particles with adsorbed mycobacterial antigens into the footpads of sensitized BALB/c mice (immune [I]-MGC), or by nitrocellulose administration to non-sensitized mice (foreign body [FB]-MGC). The development of granulomas with a highly enriched MGC population was observed 2 weeks after the nitrocellulose injection. MGC were larger with a greater number of nuclei in I-MGC than in FB-MGC. From days 7-28 after nitrocellulose administration, the production of interleukin-1alpha (IL-1alpha) and tumour necrosis factor-alpha (TNF-alpha) was demonstrated in both MGC types by in situ reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. After 2 months, the MGC had ceased production of IL-1alpha and TNF-alpha, but the expression of transforming growth factor-beta (TGF-beta) was very high, occurring together with extensive fibrosis. These results suggest that MGC are an active source of inflammatory cytokines, which can contribute to the initiation, maintenance and down-regulation of granulomatous inflammation induced by immunological and inert substances.
Insights
Multinucleated giant cells (MGC) are key players in granulomas. This study reveals MGC actively produce inflammatory cytokines like IL-1alpha and TNF-alpha, influencing granulomatous inflammation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Multinucleated giant cells (MGC) are characteristic of granulomas.
- Their precise function in granulomatous inflammation remains incompletely understood.
Purpose of the Study:
- To investigate the in vivo production and function of MGC in granuloma formation.
- To characterize the cytokine profiles of MGC in response to immunological and inert stimuli.
Main Methods:
- Developed a novel in vivo method for MGC production using nitrocellulose particles in BALB/c mice.
- Utilized in situ reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry to detect cytokine expression.
- Distinguished between immune (I)-MGC and foreign body (FB)-MGC.
Main Results:
- Granulomas with enriched MGC populations formed within 2 weeks.
- I-MGC were larger and multinucleated compared to FB-MGC.
- MGC produced interleukin-1alpha (IL-1alpha) and tumour necrosis factor-alpha (TNF-alpha) between days 7-28.
- After 2 months, MGC showed high transforming growth factor-beta (TGF-beta) expression and induced fibrosis.
Conclusions:
- MGC are active producers of inflammatory cytokines, contributing to granuloma initiation and maintenance.
- MGC play a role in the down-regulation of granulomatous inflammation through TGF-beta production and fibrosis.
- This study provides new insights into the dynamic function of MGC in immune responses.
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