Lidell Martin E, Bara Jacques, Hansson Gunnar C
Department of Medical Biochemistry, Göteborg University, Sweden.
FEBS J. 2008 Feb;275(3):481-9. doi: 10.1111/j.1742-4658.2007.06215.x. Epub 2007 Dec 21.
Mucins are large glycoproteins protecting mucosal surfaces throughout the body. Their expressions are tissue-specific, but in disease states such as cystic fibrosis, inflammation and cancer, this specificity can be disturbed. MUC5AC is normally expressed in the mucous cells of the epithelia lining the stomach and the trachea, where it constitutes a major component of the gastric and respiratory mucus. A number of mAbs have been raised against the gastric M1 antigen, an early marker for colonic carcinogenesis. Several of these mAbs recognize epitopes present on MUC5AC, suggesting that MUC5AC is the antigen. However, some of the mAbs raised against the gastric M1 antigen are widely used as antibodies against MUC5AC, despite the fact that their specificity for MUC5AC has not been clearly shown. In this study, we have tested the reactivity of the latter antibodies against a recombinantly expressed C-terminal cysteine-rich part of human MUC5AC. We demonstrate for the first time that the widely used mAb 45M1, as well as 2-12M1 and 166M1, are true antibodies against MUC5AC, with epitopes located in the C-terminal cysteine-rich part of the mucin.
粘蛋白是一种大型糖蛋白，可保护全身的粘膜表面。它们的表达具有组织特异性，但在诸如囊性纤维化、炎症和癌症等疾病状态下，这种特异性可能会受到干扰。MUC5AC通常表达于胃和气管内衬上皮的粘液细胞中，是胃和呼吸道粘液的主要成分。已经产生了许多针对胃M1抗原的单克隆抗体，胃M1抗原是结肠癌发生的早期标志物。其中一些单克隆抗体识别MUC5AC上存在的表位，这表明MUC5AC就是该抗原。然而，尽管针对胃M1抗原产生的一些单克隆抗体对MUC5AC的特异性尚未明确显示，但它们仍被广泛用作抗MUC5AC的抗体。在本研究中，我们测试了后一种抗体对重组表达的人MUC5AC富含半胱氨酸的C末端部分的反应性。我们首次证明，广泛使用的单克隆抗体45M1以及2-12M1和166M1是针对MUC5AC的真正抗体，其表位位于粘蛋白富含半胱氨酸的C末端部分。
