Kuwabara I, Liu F T
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
J Immunol. 1996 May 15;156(10):3939-44.
Galectin-3 is a member of a growing family of animal lectins composed of three domains, with the amino-terminal half consisting of a short segment followed by tandem repeats, and the carboxyl-terminal half representing the carbohydrate-recognition domain. Previously, we have shown that galectin-3 binds to the surface of human neutrophils and is capable of activating these cells. We have now studied the effect of exogenous galectin-3 on adhesion of human neutrophils to laminin-coated microtiter plates and found that this lectin promotes the adhesion in a dose-dependent manner. The effect was dependent on the lectin's carbohydrate-binding function, as well as its amino-terminal region. The galectin-3-induced adhesion was reduced significantly in the presence of EDTA, even though Ca2+ and Mg2+ are not required for the lectin binding, and the adhesion was significantly less at 4 degrees C, as compared with 37 degrees C. Galectin-3 also induced neutrophil adhesion to fibronectin, which is not recognized by the lectin, but much higher concentrations of the lectin were required, and the effect is completely dependent on Ca2+ and Mg2+. We conclude that galectin-3 induces neutrophil adhesion to laminin through a combination of two distinct mechanisms: 1) the lectin bridges neutrophils to laminin, in a carbohydrate-dependent and Ca2+-, Mg2+-independent manner, and 2) the lectin induces activation of neutrophils, in the presence of the divalent cations, resulting in the positive regulation of other cell adhesion molecules and enhanced adhesion to laminin. The results suggest that galectin-3 may play a role in the traversing of neutrophils through the basement membrane at inflammation sites.
半乳糖凝集素-3是一个不断壮大的动物凝集素家族的成员，由三个结构域组成，其氨基末端的一半由一个短片段和串联重复序列组成，羧基末端的一半代表碳水化合物识别结构域。此前，我们已经表明半乳糖凝集素-3与人类中性粒细胞表面结合，并能够激活这些细胞。我们现在研究了外源性半乳糖凝集素-3对人类中性粒细胞与层粘连蛋白包被的微量滴定板黏附的影响，发现这种凝集素以剂量依赖的方式促进黏附。这种作用依赖于凝集素的碳水化合物结合功能及其氨基末端区域。尽管凝集素结合不需要Ca2+和Mg2+，但在EDTA存在的情况下，半乳糖凝集素-3诱导的黏附显著降低，并且与37℃相比，在4℃时黏附明显减少。半乳糖凝集素-3还诱导中性粒细胞与纤连蛋白黏附，而纤连蛋白不被该凝集素识别，但需要更高浓度的凝集素，并且这种作用完全依赖于Ca2+和Mg2+。我们得出结论，半乳糖凝集素-3通过两种不同机制的组合诱导中性粒细胞与层粘连蛋白黏附：1）凝集素以碳水化合物依赖且不依赖Ca2+、Mg2+的方式将中性粒细胞与层粘连蛋白连接起来；2）在二价阳离子存在的情况下，凝集素诱导中性粒细胞活化，导致其他细胞黏附分子的正向调节并增强对层粘连蛋白的黏附。结果表明，半乳糖凝集素-3可能在炎症部位中性粒细胞穿越基底膜的过程中发挥作用。
