Lung Research Laboratory, Hanson Institute and Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia.
J Heart Lung Transplant. 2011 May;30(5):589-95. doi: 10.1016/j.healun.2011.01.710.
Mannose binding lectin (MBL) is a key mediator of both innate immunity and efferocytosis (phagocytosis of apoptotic cells) in the airway. Defective efferocytosis results in a net increase in apoptotic material that can undergo secondary necrosis, leading to tissue damage and chronic inflammation. We have shown reduced MBL and efferocytosis in other chronic inflammatory lung diseases; we therefore hypothesized that reduced MBL and efferocytosis in the airways may be a determinant of bronchiolitis obliterans syndrome (BOS) after lung transplantation.
We investigated MBL (enzyme-linked immunosorbent assay [ELISA]), MBL-mediated complement deposition (UC4, ELISA), and efferocytosis of apoptotic bronchial epithelial cells (flow cytometry) in bronchoalveolar lavage (BAL) and peripheral blood from 75 lung transplant recipients, comprising 16 with stable graft function, 34 stable with proven infection, 25 with BOS, and 14 healthy controls.
In plasma, MBL levels were highly variable (0-17.538 μg/ml), but increased in infected patients vs control (p = 0.09) or stable groups (p = 0.003). There was a similar increase in UC4 in infected patients and a significant correlation between MBL and UC4. There was no correlation between MBL and time after transplant. In BAL, MBL levels were less variable (0-73.3 ng/ml) and significantly reduced in patients with BOS vs controls and stable groups. Efferocytosis was significantly reduced in the BOS group vs control and stable groups (mean [SEM] control, 20% [1.3%]; stable, 20.5% [2.5%]; infected, 17.3% [2.8%]; BOS, 11.3% [1.5%], p = 0.04).
Low levels of MBL in the airway may play a role in reduced efferocytosis, subsequent tissue damage, and BOS after lung transplantation.
甘露糖结合凝集素（MBL）是气道固有免疫和吞噬作用（凋亡细胞的吞噬作用）的关键介质。吞噬作用缺陷会导致凋亡物质净增加，这些物质可能会发生继发性坏死，导致组织损伤和慢性炎症。我们已经在其他慢性炎症性肺部疾病中发现 MBL 和吞噬作用降低；因此，我们假设气道中 MBL 和吞噬作用降低可能是肺移植后闭塞性细支气管炎综合征（BOS）的决定因素。
我们研究了 75 名肺移植受者的支气管肺泡灌洗液（BAL）和外周血中的 MBL（酶联免疫吸附试验 [ELISA]）、MBL 介导的补体沉积（UC4，ELISA）和凋亡的支气管上皮细胞的吞噬作用（流式细胞术），其中包括 16 名稳定的移植物功能患者、34 名稳定的感染患者、25 名 BOS 患者和 14 名健康对照者。
在血浆中，MBL 水平变化很大（0-17.538μg/ml），但感染患者的 MBL 水平高于对照组（p=0.09）或稳定组（p=0.003）。感染患者的 UC4 也有类似的增加，MBL 和 UC4 之间存在显著相关性。MBL 与移植后时间之间无相关性。在 BAL 中，MBL 水平变化较小（0-73.3ng/ml），BOS 患者的 MBL 水平明显低于对照组和稳定组。与对照组和稳定组相比，BOS 组的吞噬作用明显降低（平均[SEM]对照组 20%[1.3%]；稳定组 20.5%[2.5%]；感染组 17.3%[2.8%]；BOS 组 11.3%[1.5%]，p=0.04）。
气道中 MBL 水平低可能在吞噬作用降低、随后的组织损伤和肺移植后的 BOS 中起作用。
