Galectin-3 (Gal-3) 与许多疾病/病症中的先天免疫细胞激活有关。我们发现了一种独特的反应，即人类嗜碱性粒细胞与 A549 细胞（一种肺腺癌）共培养时会分泌 IL-4/IL-13。虽然显示的参数与标准 IgE 依赖性激活一致，但这些 Galectin-3 依赖性反应是在缺乏特定 IgE/过敏原且需要细胞间接触的情况下发生的。我们现在假设这种激活模式也会影响 A549 的功能。我们的研究结果表明，嗜碱性粒细胞/A549 共培养物中会诱导细胞因子，特别是 IL-6，而单独培养任一细胞时均检测不到。如先前针对 IL-4/IL-13 所示，IL-6 的产生也需要细胞间接触，并且依赖于 A549-Gal-3，因为缺乏这种凝集素的克隆诱导的细胞因子较少。使用培养物衍生的嗜碱性粒细胞 (CDBA)，我们证明在 CDBA/A549 共培养物中诱导 IL-6 反应和另一种致瘤因子 VEGF-A 的产生，但仅在用 IgE 以某种方式被动敏化 CDBA 后才被诱导。与IL-4/IL-13相似。然而，单独培养的嗜碱性粒细胞/CDBA的IgE依赖性激活未能诱导IL-6/VEGF。重要的是，IL-3 引发的嗜碱性粒细胞，即使是用多聚甲醛固定的嗜碱性粒细胞，也很容易在共培养物中诱导 IL-6/VEGF-A，从而验证这些细胞因子源自 A549。总体而言，这些结果表明了一种复杂的机制，IL-3 引发的嗜碱性粒细胞和 A549 之间的 Gal-3/IgE 相互作用有可能调节两种细胞的细胞因子产生。 Gal-3 与从哮喘到癌症等许多疾病有关，而且与伤口愈合等正常生理条件有关，预计这些发现将有助于深入了解这种凝集素（和 IgE）在这些过程中发挥作用的分子机制。 © 作者 2024。由牛津大学出版社代表白细胞生物学学会出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

Galectin-3 (Gal-3) is implicated in innate immune cell activation in a host of diseases/conditions. We identified a unique response whereby human basophils secrete IL-4/IL-13 when co-cultured with A549 cells -a lung adenocarcinoma. While displaying parameters consistent with standard IgE-dependent activation, these Galectin-3-dependent responses occurred in the absence of specific IgE/allergen and required cell-to-cell contact. We now hypothesize that this mode of activation also impacts A549 function. Our findings show that cytokines are induced in basophil/A549 co-cultures that are not detected when either cell is cultured alone, in particular IL-6. As previously shown for IL-4/IL-13, IL-6 production also required cell-to-cell contact and was dependent on A549-Gal-3, since clones deficient of this lectin induced less cytokine. Using culture-derived basophils (CDBA), we demonstrate that the IL-6 response, and production of another tumorigenic factor, VEGF-A, are induced in CDBA/A549 co-cultures but only after passively sensitizing CDBA with IgE, in a manner similar to IL-4/IL-13. However, IgE-dependent activation of basophils/CDBA cultured alone failed to induce IL-6/VEGF. Importantly, IL-3-primed basophils, even those fixed with paraformaldehyde, readily induced IL-6/VEGF-A in co-cultures, thus verifying these cytokines are derived from A549. Overall, these results suggest a complex mechanism whereby Gal-3/IgE interactions between IL-3-primed basophils and A549 have the potential to modulate cytokine production by both cells. With Gal-3 implicated in many diseases ranging from asthma to cancer, but also in normal physiological conditions, such as wound healing, these findings are predicted to provide insight into the molecular mechanisms by which this lectin (and IgE) functions in these processes.© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.