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In vitro expression of IL-1α, GM-CSF, and TNF-α by multinucleated macrophages from BCG-infected mice
D A Iljine1, S A Arkhipov, V A Shkurupy
1Research Center of Clinical and Experimental Medicine, Siberian Division of the Russian Academy of Medical Sciences; Novosibirsk State Medical University, Russia. arkhipov@soramn.ru.
Abstract:
Peritoneal cells from intact and BCG-infected mice were explanted in vitro. In these cultures, multinucleated macrophages in different number of nuclei were formed. The intensity of multinucleated cell formation was higher in cultures from BCG-infected mice. Increasing role of amitosis in the formation of multinucleated macrophages with relatively high number of nuclei was noted with presumable domination of cell fusion mechanism. Relatively high level of IL-1α expression was noted only in the population of binucleated macrophages of BCG-infected mice in comparison with mononuclear cells. It was found macrophages from BCG-infected mice demonstrate a kind of "lineage commitment" towards multinucleated cells, which manifested in culture in initially high and increasing (with increasing the number of nuclei in cells) expression of granulocyte-macrophage CSF and TNF-α as well as initially high amitotic activity of macrophages.
Insights
BCG infection enhances multinucleated macrophage formation in mice via increased amitosis and cell fusion. Binucleated macrophages show higher IL-1α expression, indicating a lineage commitment towards multinucleated cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophage differentiation and multinucleation are crucial immune processes.
- Bacillus Calmette-Guérin (BCG) infection is known to modulate macrophage behavior.
Purpose of the Study:
- To investigate the mechanisms of multinucleated macrophage formation in vitro.
- To compare multinucleated cell formation in intact versus BCG-infected mice.
- To analyze the role of amitosis and cell fusion in this process.
Main Methods:
- Explantation of peritoneal cells from intact and BCG-infected mice.
- In vitro culture of explanted cells to observe multinucleated macrophage formation.
- Analysis of multinucleated cell formation intensity and mechanisms (amitosis, fusion).
- Assessment of Interleukin-1 alpha (IL-1α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and Tumor Necrosis Factor-alpha (TNF-α) expression.
Main Results:
- Multinucleated macrophages with varying numbers of nuclei were formed in vitro.
- BCG-infected mice showed a higher intensity of multinucleated cell formation compared to intact mice.
- Amitosis played an increasing role in forming multinucleated macrophages with more nuclei, alongside cell fusion.
- Binucleated macrophages from BCG-infected mice exhibited elevated IL-1α expression compared to mononuclear cells.
- Macrophages from BCG-infected mice displayed "lineage commitment" towards multinucleated cells, evidenced by high GM-CSF and TNF-α expression and amitotic activity.
Conclusions:
- BCG infection promotes multinucleated macrophage formation through enhanced amitosis and cell fusion.
- Binucleated macrophages in BCG-infected mice are characterized by increased IL-1α expression.
- Macrophages from BCG-infected mice exhibit a predisposition towards multinucleation, indicated by cytokine expression and cellular behavior.
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