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Interleukin-13 induces human monocyte/macrophage fusion and macrophage mannose receptor expression
K M DeFife1, C R Jenney, A K McNally
1Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Abstract:
Inasmuch as we recently demonstrated that IL-4 is a strong inducer of monocyte/macrophage fusion and IL-13 has been observed to mimic many of the biologic effects of IL-4, the ability of IL-13 to promote human macrophage fusion in vitro was tested and compared with IL-4-mediated fusion. IL-13 induced the fusion of monocyte-derived macrophages as potently as IL-4 under identical culture conditions, and resulted in foreign body-type giant cell formation. At optimal concentrations of cytokine added, statistically equal numbers of macrophages participated in IL-13- and IL-4-induced fusion (66.1 +/- 4.6% and 63.9 +/- 4.4%, respectively). However, the effects of IL-13 and IL-4 were not additive or synergistic, and the maximum fusion obtained when both IL-4 and IL-13 were added was 63.8 +/- 3.6%. Only anti-human IL-13 Abs inhibited IL-13-induced foreign body giant cell formation; the fusion-inducing effects of IL-13 continued to be observed in the presence of neutralizing Abs to IL-4 and several other anti-cytokine Abs, including Abs against IFN-gamma, granulocyte-macrophage CSF, IL-3, and TNF-alpha. IL-13 also significantly enhanced the fluorescence intensity detected by anti-human macrophage mannose receptor Abs, indicating that IL-13, like IL-4, up-regulates expression of the receptor that may be an essential participant in macrophage fusion. The results of this study demonstrate that IL-13, like IL-4, is a potent human macrophage fusion factor, and suggest that although IL-13 acts independently of IL-4 to promote foreign body giant cell formation, it may trigger a common mechanism for macrophage fusion.
Insights
Interleukin-13 (IL-13) effectively induces human macrophage fusion, similar to Interleukin-4 (IL-4). This suggests IL-13 acts independently to promote giant cell formation, potentially via a shared fusion pathway.
Area of Science:
- Immunology
- Cell Biology
- Cytokine Signaling
Background:
- Interleukin-4 (IL-4) is a known potent inducer of monocyte/macrophage fusion.
- Interleukin-13 (IL-13) shares many biological effects with IL-4.
- The role of IL-13 in human macrophage fusion has not been fully elucidated.
Purpose of the Study:
- To investigate the ability of IL-13 to promote human macrophage fusion in vitro.
- To compare the fusion-inducing capacity of IL-13 with that of IL-4.
- To explore the mechanism of IL-13-mediated macrophage fusion.
Main Methods:
- In vitro culture of monocyte-derived macrophages.
- Treatment with IL-13 and/or IL-4 cytokines.
- Quantification of macrophage fusion and giant cell formation.
- Assessment of macrophage mannose receptor expression.
- Inhibition studies using neutralizing antibodies against various cytokines.
Main Results:
- IL-13 induced human macrophage fusion as potently as IL-4, forming foreign body-type giant cells.
- Optimal concentrations of IL-13 and IL-4 resulted in statistically similar fusion rates (66.1% vs. 63.9%).
- IL-13 and IL-4 effects were not additive or synergistic; combined maximal fusion was 63.8%.
- Anti-IL-13 antibodies inhibited IL-13-induced fusion, while anti-IL-4 antibodies did not.
- IL-13 up-regulated macrophage mannose receptor expression, similar to IL-4.
Conclusions:
- IL-13 is a potent inducer of human macrophage fusion, comparable to IL-4.
- IL-13 promotes foreign body giant cell formation through a mechanism independent of IL-4.
- IL-13 may utilize a common pathway for macrophage fusion, potentially involving mannose receptor upregulation.