低浓度重复注射脂磷壁酸通过 IL-6/STAT3 信号通路激活适应性免疫反应诱导囊状收缩。
Repeated Lipoteichoic Acid Injection at Low Concentration Induces Capsular Contracture by Activating Adaptive Immune Response through the IL-6/STAT3 Signaling Pathway.
机构信息
From the Department of Plastic Surgery, Zhongshan Hospital, Fudan University.
Treatment Center of Burn and Trauma, Affiliated Hospital of Jiangnan University, Jiangnan University.
出版信息
Plast Reconstr Surg. 2023 Aug 1;152(2):349-359. doi: 10.1097/PRS.0000000000010224. Epub 2023 Jan 26.
BACKGROUND
Capsular contracture is the most common complication of breast implantation surgery. Bacterial contamination was considered to play an important role in the occurrence of capsular contracture, and Gram-positive bacteria such as Staphylococcus epidermidis were discovered in the clinical specimens. Lipoteichoic acid (LTA) was a component of the cell wall of Gram-positive bacteria and was sufficient in the pathogenicity of the bacteria. The authors assumed that LTA could trigger the immunologic response against the implant and cause capsular contracture.
METHODS
The authors developed a rat model of capsular contracture by repeated injection of 10 μg/mL LTA. The histologic changes of the capsule tissue were measured by hematoxylin and eosin, sirius red, Masson, and immunohistochemical staining. The expression of related cytokines was measured by quantitative real-time polymerase chain reaction. The downstream pathway activation was shown by Western blot. The authors also applied tocilizumab, an interleukin (IL)-6 receptor antagonist, to verify the role of IL-6 in this pathologic process.
RESULTS
The authors discovered that repeated LTA injection, at a low concentration, could induce the thickening of capsule tissue, the deposition of collagen fiber, and the activation of myofibroblasts. The IL-6/signal transducer and activator of transcription 3 signaling pathway was activated in this process, and the inhibition of IL-6 receptor could relieve the symptoms. B cells and T-helper cells, especially T-helper type 1, could be related to this phenomenon.
CONCLUSIONS
The authors' research corroborated that subclinical infection could trigger capsular contracture, and the immune system played an important role in this process. The authors' results provided a possible research direction for the mechanism of bacterial infection-induced immune response against breast implants.
CLINICAL RELEVANCE STATEMENT
The authors' research provides a possible research direction for the mechanism of bacterial infection-induced immune response against breast implants, and a potential target for predicting the prognosis of capsular contracture.
背景
包膜挛缩是乳房植入手术最常见的并发症。细菌污染被认为在包膜挛缩的发生中起重要作用,并且在临床标本中发现了表皮葡萄球菌等革兰氏阳性菌。脂磷壁酸(LTA)是革兰氏阳性菌细胞壁的组成部分,在细菌的致病性中起着重要作用。作者假设 LTA 可以引发针对植入物的免疫反应,导致包膜挛缩。
方法
作者通过重复注射 10μg/ml LTA 建立了大鼠包膜挛缩模型。通过苏木精和伊红、天狼星红、马松和免疫组织化学染色测量胶囊组织的组织学变化。通过定量实时聚合酶链反应测量相关细胞因子的表达。通过 Western blot 显示下游途径的激活。作者还应用托珠单抗,一种白细胞介素(IL)-6 受体拮抗剂,验证 IL-6 在这一病理过程中的作用。
结果
作者发现,低浓度的重复 LTA 注射可导致胶囊组织增厚、胶原纤维沉积和肌成纤维细胞激活。在此过程中,IL-6/信号转导和转录激活因子 3 信号通路被激活,抑制 IL-6 受体可缓解症状。B 细胞和辅助性 T 细胞,特别是辅助性 T 细胞 1,可能与这一现象有关。
结论
作者的研究证实了亚临床感染可引发包膜挛缩,免疫系统在这一过程中起着重要作用。作者的研究结果为细菌感染引起的针对乳房植入物的免疫反应机制提供了一个可能的研究方向。
临床相关性声明
作者的研究为细菌感染引起的针对乳房植入物的免疫反应机制提供了一个可能的研究方向,也为预测包膜挛缩的预后提供了一个潜在的目标。