Alcohol Research Program, Stritch School of Medicine, Loyola University Chicago Health Sciences Campus, 2160 S. 1st Ave., Maywood, IL, 60153, United States; Burn and Shock Trauma Research Institute, Stritch School of Medicine, Loyola University Health Sciences Campus, 2160 S. 1st Ave., Maywood, IL, 60153, United States.
Burn and Shock Trauma Research Institute, Stritch School of Medicine, Loyola University Health Sciences Campus, 2160 S. 1st Ave., Maywood, IL, 60153, United States.
Alcohol. 2019 Nov;80:109-117. doi: 10.1016/j.alcohol.2018.11.003. Epub 2018 Nov 9.
The relatively low long-term survival rate of lung transplant recipients as compared to other organ recipients serves as an impetus to identify potential lung dysfunction as early as possible. There is an association between donor heavy alcohol use and acute lung injury in the lung allograft after transplant, known as primary graft dysfunction. Excessive alcohol use (EAU) can induce pulmonary immune dysregulation in response to an infection. Antimicrobial peptides (AMPs) are an important component of the innate immune response to pulmonary infections, but the impact of EAU on AMPs in the allograft lung has not been evaluated. Our hypothesis is that specific lung AMPs, LL-37, α-defensin-1,2,3, and β-defensin-2, are dysregulated in the lungs from organ donors who had EAU. In this prospective observational investigation, we measured AMPs via ELISA and inflammatory cytokines via multiplex bead array, in bronchoalveolar lavage (BAL) fluid of lung allograft donors, comparing results based on their alcohol consumption. LL-37 levels in lung donors with EAU were found to be increased compared to nondrinker (ND) donors [median 7.7 ng/mL (IQR 4.1-37.0) vs. 2.3 ng/mL (IQR 1.1-7.9), p = 0.004], whereas α-defensins-1,2,3 were decreased only in the presence of an infection in donors with EAU compared to ND donors [median 2.2 ng/mL (IQR 1.6-2.4) vs. 3.2 ng/mL (IQR 2.3-3.8), p = 0.049]. There was no difference in β-defensin-2 levels. Gene expression levels of these AMPs were not different. Elevated levels of CXCL8 were noted in bronchial washings of donors with EAU compared to ND donors, [median 4372 pg/mL (IQR 3352-13180) vs. 867.3 pg/mL (IQR 163.6-3675), p = 0.04], suggesting a potentially heightened inflammatory response. At 1 month post-transplant, LL-37 and CXCL8 levels are decreased compared to levels at time of transplant. In lung donors with EAU, LL-37 and α-defensins-1,2,3 dysregulated levels in the presence of an infection may be a harbinger of dysfunction of the lungs through the transplant process.
与其他器官接受者相比，肺移植受者的长期生存率相对较低，这促使人们尽早发现潜在的肺功能障碍。在移植后的肺移植物中，供体大量饮酒与急性肺损伤有关，称为原发性移植物功能障碍。过量饮酒（EAU）可导致肺部免疫失调，从而引发肺部感染。抗菌肽（AMPs）是肺部感染固有免疫反应的重要组成部分，但 EAU 对同种异体肺中的 AMP 的影响尚未得到评估。我们的假设是，在 EAU 供体的肺中，特定的肺 AMPs（LL-37、α-防御素-1、2、3 和β-防御素-2）会失调。在这项前瞻性观察研究中，我们通过 ELISA 测量了支气管肺泡灌洗液（BAL）中肺移植物供体的 AMPs，并通过多重微珠阵列测量了炎症细胞因子，根据他们的饮酒情况比较了结果。与非饮酒（ND）供体相比，EAU 供体的肺中 LL-37 水平升高[中位数 7.7ng/mL（IQR 4.1-37.0）与 2.3ng/mL（IQR 1.1-7.9），p=0.004]，而仅在 EAU 供体存在感染的情况下，α-防御素-1、2、3 才会降低与 ND 供体相比[中位数 2.2ng/mL（IQR 1.6-2.4）与 3.2ng/mL（IQR 2.3-3.8），p=0.049]。β-防御素-2 水平没有差异。这些 AMP 的基因表达水平没有差异。与 ND 供体相比，EAU 供体的支气管灌洗液中 CXCL8 水平升高[中位数 4372pg/mL（IQR 3352-13180）与 867.3pg/mL（IQR 163.6-3675），p=0.04]，表明炎症反应可能加剧。在移植后 1 个月，LL-37 和 CXCL8 水平与移植时相比降低。在 EAU 供体中，感染时 LL-37 和 α-防御素-1、2、3 失调水平可能预示着肺部通过移植过程发生功能障碍。
