Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
Section Mass Spectrometry and Proteomics, Diagnostic Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Int J Mol Sci. 2022 Dec 6;23(23):15359. doi: 10.3390/ijms232315359.
The polypeptide TFF3 belongs to the trefoil factor family (TFF) of lectins. TFF3 is typically secreted from mucous epithelia together with mucins. Both intestinal and salivary TFF3 mainly exist as disulfide-linked heterodimers with IgG Fc binding protein (FCGBP). Here, we investigated bronchial tissue specimens, bronchial secretions, and bronchoalveolar lavage (BAL) fluid from patients with a chronic obstructive pulmonary disease (COPD) background by fast protein liquid chromatography and proteomics. For the first time, we identified different molecular forms of TFF3 in the lung. The high-molecular mass form represents TFF3-FCGBP oligomers, whereas the low-molecular mass forms are homodimeric and monomeric TFF3 with possibly anti-apoptotic activities. In addition, disulfide-linked TFF3 heterodimers with an M of about 60k and 30k were detected in both bronchial secretions and BAL fluid. In these liquids, TFF3 is partly -terminally truncated probably by neutrophil elastase cleavage. TFF3-FCGBP is likely involved in the mucosal innate immune defense against microbial infections. We discuss a hypothetical model how TFF3 might control FCGBP oligomerization. Furthermore, we did not find indications for interactions of TFF3-FCGBP with DMBT1gp or the mucin MUC5AC, glycoproteins involved in mucosal innate immunity. Surprisingly, bronchial MUC5AC appeared to be degraded when compared with gastric MUC5AC.
多肽 TFF3 属于三叶因子家族（TFF）的凝集素。TFF3 通常与粘蛋白一起从粘膜上皮分泌。肠和唾液中的 TFF3 主要以与 IgG Fc 结合蛋白（FCGBP）形成二硫键连接的异二聚体形式存在。在这里，我们通过快速蛋白质液相等技术，对患有慢性阻塞性肺疾病（COPD）背景的患者的支气管组织标本、支气管分泌物和支气管肺泡灌洗液（BAL）进行了研究。我们首次在肺部鉴定出 TFF3 的不同分子形式。高分子量形式代表 TFF3-FCGBP 寡聚物，而低分子量形式是具有潜在抗凋亡活性的同二聚体和单体 TFF3。此外，在支气管分泌物和 BAL 液中均检测到二硫键连接的 TFF3 异二聚体，其分子量约为 60k 和 30k。在这些液体中，TFF3 可能通过中性粒细胞弹性蛋白酶切割而部分 N 端截断。TFF3-FCGBP 可能参与粘膜先天免疫防御微生物感染。我们讨论了一个假设模型，说明 TFF3 如何控制 FCGBP 寡聚化。此外，我们没有发现 TFF3-FCGBP 与 DMBT1gp 或粘蛋白 MUC5AC 相互作用的迹象，DMBT1gp 和 MUC5AC 是参与粘膜先天免疫的糖蛋白。令人惊讶的是，与胃 MUC5AC 相比，支气管 MUC5AC 似乎被降解。
