title: The concentration-dependent chemokine release and pro-apoptotic effects of neutrophil-derived alpha-defensin-1 on human bronchial and alveolar epithelial cells.
abstract: Defensins play a pivotal role in antimicrobial reactions, inflammatory responses, wound repair, and specific immunity. In inflammatory and infectious lung diseases, alpha-defensins are released from recruited neutrophils, and modulate a variety of lung cell functions. We found that human bronchial and alveolar epithelial cells treated with low and moderate concentrations (5 and 10 micro g/ml) of purified neutrophil-derived alpha-defensin-1 secreted more interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 in a dose- and time-dependent manner. Under moderate and high concentrations (10 and 20 micro g/ml) of alpha-defensin-1, we observed typical apoptotic changes in the lung epithelial cells after stimulation for 24 h. Furthermore, alpha-defensin-1 triggered lung cell detachment in a time- and dose-dependent manner at moderate and high concentrations. Prior to the detachment, caspase-3 activity significantly increased. On confocal laser microscopy, rapid translocation of alpha-defensin-1 to the endoplasmic reticulum (ER) was noted. These findings suggest that neutrophil-derived alpha-defensin-1 has pro-inflammatory and apoptotic effects in human bronchial and alveolar epithelial cells, which are concentration-dependent and may be associated with ER activity.
authors.affiliation: Department of Thoracic Medicine, Chang-Gung Memorial Hospital and Chang-Gung University, Taipei, Taiwan.
authors.forename: Chien-Ying
authors.initials: CY
authors.lastname: Liu
authors.forename: Horng-Chyuan
authors.initials: HC
authors.lastname: Lin
authors.forename: Chih-Teng
authors.initials: CT
authors.lastname: Yu
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Lin
authors.forename: Kang-Yun
authors.initials: KY
authors.lastname: Lee
authors.forename: Hao-Chen
authors.initials: HC
authors.lastname: Chen
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chou
authors.forename: Chien-Da
authors.initials: CD
authors.lastname: Huang
authors.forename: Pai-Chien
authors.initials: PC
authors.lastname: Chou
authors.forename: Wen-Te
authors.initials: WT
authors.lastname: Liu
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Han-Pin
authors.initials: HP
authors.lastname: Kuo
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D023084:alpha-Defensins / Q000494:pharmacology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000890:Anti-Infective Agents; C111835:CCL2 protein, human; D061945:Caspase Inhibitors; D018932:Chemokine CCL2; D018925:Chemokines; D004338:Drug Combinations; D016209:Interleukin-8; D012333:RNA, Messenger; D023084:alpha-Defensins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C406413:human neutrophil peptide 1; D053148:Caspase 3