title: Annexin II mediates the neutrophil elastase-stimulated exocytosis of mucin 5ac.
abstract: The overexpression and hypersecretion of mucus is a hallmark of several chronic pulmonary inflammatory diseases, including chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis. Mucin 5ac (MUC5AC) is a major component of airway mucus. Annexin II (ANXII) has been reported to be expressed in various cells and is associated with the fusion of secretory vesicles. Neutrophil elastase (NE) is present at high concentrations in the airway surface fluid in patients with cystic fibrosis and various other severe diseases. However, the role of ANXII in NE-induced secretion of MUC5AC granules remains unclear. It was determined that NE upregulates the transcription and protein synthesis of ANXII in 16HBE human bronchial epithelial cells. Following stimulation with NE, ANXII is recruited to the cell membrane, as visualised by cell immunochemistry and laser confocal microscopy, and the redistribution of ANXII is inhibited by the protein kinase-C (PKC) inhibitor bisindolylmaleimide I. Conversely, depleting endogenous ANXII decreases MUC5AC secretion into the cell culture supernatant and increases the levels of intracellular MUC5AC protein. The data indicated that ANXII is associated with the secretion of MUC5AC granules.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
authors.forename: Juliy M
authors.initials: JM
authors.lastname: Perelman
authors.forename: Victor P
authors.initials: VP
authors.lastname: Kolosov
mesh_terms: D017306:Annexin A2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005089:Exocytosis; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D055271:Mucin 5AC / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D017306:Annexin A2; D055271:Mucin 5AC; D034741:RNA, Small Interfering; D019272:Leukocyte Elastase