Diebel Lawrence N, Liberati David M, Dulchavsky Scott A, Diglio Clement A, Brown William J
Department of Surgery, Wayne State University, Detroit, Mich 48201 ,USA.
Surgery. 2002 Oct;132(4):573-81; discussion 581. doi: 10.1067/msy.2002.127553.
Increased epithelial permeability may contribute to septic complications after alcohol intoxication. Prior ethanol (EtOH) exposure leads to structural and functional effects on cytoskeletal components important in maintaining barrier integrity. The cytoskeleton is also important in the transcellular transport of proteins including the polymeric immunoglobulin receptor (pIgR) mediated transport of immunoglobulin A (IgA) to the luminal surface of mucosal tissues. We (1) investigated the effects of acute EtOH exposure on cell monolayer barrier integrity and IgA transport and (2) assessed the importance of microtubule function on these functions in vitro.
Confluent Madin-Darby canine kidney (MDCK) epithelial cells transfected with pIgR cDNA were exposed to 1% or 5% EtOH, and transcytosis of dimeric IgA was measured. Paclitaxel was used to pretreat a subset of MDCK cells. Results. EtOH exposure resulted in a concentration and time dependent decrease in IgA transcytosis. This was associated with physical derangements in the integrity of the cell monolayer. Pretreatment with paclitaxel completely abrogated these effects.
EtOH causes both physical and immune derangement of epithelial cell barrier function. Decreased secretory IgA at mucosal surfaces may initiate septic complications after EtOH intoxication.
上皮通透性增加可能导致酒精中毒后的脓毒症并发症。先前的乙醇(EtOH)暴露会对维持屏障完整性至关重要的细胞骨架成分产生结构和功能影响。细胞骨架在蛋白质的跨细胞转运中也很重要,包括聚合免疫球蛋白受体(pIgR)介导的免疫球蛋白A(IgA)向粘膜组织腔表面的转运。我们(1)研究了急性EtOH暴露对细胞单层屏障完整性和IgA转运的影响,以及(2)在体外评估了微管功能对这些功能的重要性。
用pIgR cDNA转染的汇合的犬肾(MDCK)上皮细胞暴露于1%或5%的EtOH,并测量二聚体IgA的转胞吞作用。用紫杉醇预处理一部分MDCK细胞。结果。EtOH暴露导致IgA转胞吞作用呈浓度和时间依赖性降低。这与细胞单层完整性的物理紊乱有关。用紫杉醇预处理完全消除了这些影响。
EtOH导致上皮细胞屏障功能的物理和免疫紊乱。粘膜表面分泌型IgA减少可能引发EtOH中毒后的脓毒症并发症。