| Autor: |
Weste J; Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany., Houben T; Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany., Harder S; Section Mass Spectrometry and Proteomics, Diagnostic Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Schlüter H; Section Mass Spectrometry and Proteomics, Diagnostic Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Lücke E; Department of Pneumology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany., Schreiber J; Department of Pneumology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany., Hoffmann W; Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany. |
| Abstrakt: |
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 r of about 60k and 30k were detected in both bronchial secretions and BAL fluid. In these liquids, TFF3 is partly N -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 340 or the mucin MUC5AC, glycoproteins involved in mucosal innate immunity. Surprisingly, bronchial MUC5AC appeared to be degraded when compared with gastric MUC5AC. |
