Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Transl Res. 2012 Dec;160(6):435-42. doi: 10.1016/j.trsl.2012.08.003. Epub 2012 Sep 16.
Monocyte chemotactic protein-1 (MCP-1), also known as "chemokine ligand 2" (CCL2), is a monocyte-attracting chemokine produced in lung epithelial cells. We previously reported an association of increased levels of plasma MCP-1 with primary graft dysfunction (PGD) after lung transplantation in a nested case-control study of extreme phenotypes using a multiplex platform. In this study, we sought to evaluate the role of plasma MCP-1 level as a biomarker across the full spectrum of PGD. We performed a prospective cohort study of 108 lung transplant recipients within the Lung Transplant Outcomes Group cohort. Plasma MCP-1 levels were measured pretransplantation and 6 and 24 hours after transplantation. The primary outcome was development of grade 3 PGD within 72 hours of transplant, with secondary analyses at the 72-hour time point. Multivariable logistic regression was used to evaluate confounding. Thirty subjects (28%) developed PGD. Median MCP-1 measured at 24 hours post-transplant was elevated in subjects with PGD (167.95 vs 103.5 pg/mL, P = .04). MCP-1 levels at 24 hours were associated with increased odds of grade 3 PGD after lung transplantation (odds ratio for each 100 pg/mL, 1.24; 95% confidence interval, 1.00-1.53) and with grade 3 PGD present at the 72-hour time point (odds ratio for each 100 pg/mL, 1.57; 95% confidence interval, 1.18-2.08), independent of confounding variables in multivariable analyses. MCP-1 levels measured preoperatively and 6 hours after transplant were not significantly associated with PGD. Persistent elevations in MCP-1 levels at 24 hours are a biomarker of grade 3 PGD post-transplantation. Monocyte chemotaxis may play a role in the pathogenesis of PGD.
单核细胞趋化蛋白-1(MCP-1),也称为“趋化因子配体 2”(CCL2),是肺上皮细胞产生的一种吸引单核细胞的趋化因子。我们之前在使用多重平台的极端表型巢式病例对照研究中报告了血浆 MCP-1 水平升高与肺移植后原发性移植物功能障碍(PGD)之间的关联。在这项研究中,我们试图评估血浆 MCP-1 水平作为整个 PGD 谱中生物标志物的作用。我们对肺移植结局组队列中的 108 例肺移植受者进行了前瞻性队列研究。在移植前、移植后 6 小时和 24 小时测量血浆 MCP-1 水平。主要结局是移植后 72 小时内发生 3 级 PGD,在 72 小时时间点进行次要分析。使用多变量逻辑回归评估混杂因素。30 名受试者(28%)发生了 PGD。在发生 PGD 的受试者中,移植后 24 小时测量的 MCP-1 中位数升高(167.95 与 103.5 pg/mL,P=.04)。移植后 24 小时的 MCP-1 水平与肺移植后 3 级 PGD 的发生几率增加相关(每增加 100 pg/mL 的比值比为 1.24;95%置信区间为 1.00-1.53),并且与 72 小时时间点存在 3 级 PGD 相关(每增加 100 pg/mL 的比值比为 1.57;95%置信区间为 1.18-2.08),这与多变量分析中的混杂变量无关。术前和移植后 6 小时测量的 MCP-1 水平与 PGD 无显著相关性。24 小时时 MCP-1 水平持续升高是移植后 3 级 PGD 的生物标志物。单核细胞趋化可能在 PGD 的发病机制中起作用。