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Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells
1Department of Immunology, DNAX Research Institute, Palo Alto, California 94304.
Abstract:
Giant multinucleated cells (GMCs) are associated with granulomatous lesions that form in response to various infectious and noninfectious agents. The present study shows that mouse IL-4 induces the in vitro formation of GMCs by factor-dependent bone marrow and alveolar monocytes via cell fusion. GMCs appear 2 d after incubation of cell cultures with 20 U/ml or more of IL-4. Anti-IL-4 mAbs block the appearance of GMCs in these cultures, indicating that IL-4 acts directly on monocytes to promote fusion and does not secondarily induce the production of other soluble fusion factors. In soft agar cultures, IL-4 also causes the aggregation of macrophages and diminishes their migration. The role of IL-4 in a granulomatous inflammatory response is discussed.
Insights
Interleukin-4 (IL-4) directly induces giant multinucleated cells (GMCs) formation in monocytes through cell fusion. This finding is crucial for understanding granulomatous inflammation and the role of IL-4 in immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Giant multinucleated cells (GMCs) are characteristic of granulomatous lesions.
- These lesions form in response to diverse infectious and noninfectious stimuli.
Purpose of the Study:
- To investigate the role of Interleukin-4 (IL-4) in the in vitro formation of GMCs.
- To elucidate the mechanism by which IL-4 influences monocyte behavior and fusion.
Main Methods:
- Bone marrow and alveolar monocytes were cultured in vitro.
- Cells were incubated with varying concentrations of mouse IL-4.
- Inhibition studies were performed using anti-IL-4 monoclonal antibodies (mAbs).
- Soft agar cultures were used to assess macrophage aggregation and migration.
Main Results:
- IL-4 induced the formation of GMCs from monocytes via cell fusion at concentrations of 20 U/ml or higher.
- Anti-IL-4 mAbs effectively blocked GMC formation, confirming IL-4's direct action.
- IL-4 promoted macrophage aggregation and reduced their migration in soft agar cultures.
Conclusions:
- IL-4 directly promotes monocyte fusion, leading to GMC formation.
- IL-4 plays a significant role in modulating macrophage behavior relevant to granulomatous inflammation.