Diebel Lawrence N, Liberati David M, Diglio Clement A, Brown William J
Department of Surgery, Wayne State University Health Center, Detroit, Michigan 48201, USA.
J Trauma. 2005 Nov;59(5):1099-106. doi: 10.1097/01.ta.0000187797.38327.78.
Preservation of mucosal immunity has been shown to affect the risk and outcome of pneumonia in severely injured patients. Secretory immunoglobulin A (SIgA) is the principle humoral defense of mucosal surfaces in the body and has several antiinflammatory properties. Polymorphonuclear neutrophils (PMN) function to kill invading microorganisms, but their exaggerated inflammatory responses may cause tissue injury to the host. The purpose of this study was to compare the ability of different immunoglobulin (Ig) isotypes to modulate PMN cytotoxic potential cocultured with respiratory epithelial cells challenged with bacteria.
Calu-3 cell monolayers were established on membranes (0.1-microm pore) in a two-chamber culture system. Escherichia coli (EC) incubated with either polyclonal SIgA or IgG was inoculated into the apical chamber and PMNs (10/mL) added to the basal chamber. PMN cytotoxic potential was indexed by % CD11b expression, superoxide anion (O2) production, and elastase release. Dextran flux was used to index Calu-3 monolayer permeability.
Addition of EC to PMN-Calu-3 cell coculture increased % CD11b expression, O2 production, and elastase release. IgG had no effect on PMN activation after EC challenge. SIgA abrogated PMN activation and the increase in Calu-3 cell monolayer permeability noted with EC or EC + IgG treatment groups.
PMN cytotoxic potential was decreased by the presence of SIgA but not IgG in an in vitro model to simulate pneumonia in vivo. SIgA may not only function to protect against microbial invasion of mucosal surfaces, but may also protect against tissue injury from an exaggerated inflammatory response.
已有研究表明，维持黏膜免疫会影响重症创伤患者发生肺炎的风险及预后。分泌型免疫球蛋白A（SIgA）是机体黏膜表面主要的体液防御物质，具有多种抗炎特性。多形核中性粒细胞（PMN）的功能是杀灭入侵的微生物，但其过度的炎症反应可能会对宿主造成组织损伤。本研究旨在比较不同免疫球蛋白（Ig）同种型调节与受细菌攻击的呼吸道上皮细胞共培养的PMN细胞毒性潜能的能力。
在双室培养系统的膜（0.1微米孔径）上建立Calu-3细胞单层。将与多克隆SIgA或IgG孵育的大肠杆菌（EC）接种到顶室，并将PMN（10/mL）添加到底室。通过CD11b表达百分比、超氧阴离子（O2）产生量和弹性蛋白酶释放量来衡量PMN细胞毒性潜能。用葡聚糖通量来衡量Calu-3单层的通透性。
将EC添加到PMN-Calu-3细胞共培养体系中会增加CD11b表达百分比、O2产生量和弹性蛋白酶释放量。EC攻击后，IgG对PMN激活没有影响。SIgA可消除PMN激活以及EC或EC+IgG处理组中Calu-3细胞单层通透性的增加。
在模拟体内肺炎的体外模型中，SIgA的存在可降低PMN细胞毒性潜能，而IgG则无此作用。SIgA不仅可能起到防止微生物侵袭黏膜表面的作用，还可能防止过度炎症反应造成的组织损伤。
