Magallón María, Castillo-Corullón Silvia, Bañuls Lucía, Romero Teresa, Pellicer Daniel, Herrejón Alberto, Navarro-García María Mercedes, González Cruz, Dasí Francisco
Department of Physiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez, 15, 46010 Valencia, Spain.
Instituto de Investigación Sanitaria INCLIVA, Rare Respiratory Diseases Group, Avda. Menéndez y Pelayo, 4, 46010 Valencia, Spain.
Antioxidants (Basel). 2024 Sep 2;13(9):1071. doi: 10.3390/antiox13091071.
Alpha-1 antitrypsin deficiency (AATD) is an inflammatory disorder where neutrophils play a key role. Excessive neutrophil activation leads to local hypoxia and tissue damage. Most research on neutrophil function has been conducted under atmospheric conditions (21% O), which may not represent physiological or pathological conditions. This study aimed to determine the effects of hypoxia on neutrophil degranulation and cytokine production in AATD patients.
Neutrophils isolated from 54 AATD patients (31 MZ; 8 SZ; 15 ZZ) and 7 controls (MM) were exposed to hypoxia (1% O) for 4 h. Neutrophil degranulation was assessed by measuring elastase (NE), myeloperoxidase (MPO), lactoferrin, and matrix metalloproteinase-9 (MMP-9) levels using immunoassay-based methods. Pro-inflammatory (IL-8, IL-1 beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-4 and IL-10) cytokine levels were assessed by a Luminex-based method.
Our results indicate a significantly increased release of NE ( = 0.015), MPO ( = 0.042), lactoferrin ( = 0.015), and MMP-9 ( = 0.001) compared to controls. Pro-inflammatory cytokines show a significant rise in IL-8 ( = 0.019), a trend towards increased IL-1 beta ( = 0.3196), no change in IL-6 ( = 0.7329), and reduced TNF-alpha ( = 0.006). Anti-inflammatory cytokines show increased IL-4 ( = 0.057) and decreased IL-10 ( = 0.05703).
Increased neutrophil degranulation and inflammatory phenotype are observed in AATD neutrophils under physiological hypoxia.
α-1抗胰蛋白酶缺乏症（AATD）是一种炎症性疾病，中性粒细胞在其中起关键作用。中性粒细胞过度活化会导致局部缺氧和组织损伤。大多数关于中性粒细胞功能的研究是在大气条件（21%氧气）下进行的，这可能并不代表生理或病理状况。本研究旨在确定缺氧对AATD患者中性粒细胞脱颗粒和细胞因子产生的影响。
从54例AATD患者（31例MZ；8例SZ；15例ZZ）和7例对照（MM）中分离出中性粒细胞，使其暴露于缺氧环境（1%氧气）4小时。通过基于免疫测定的方法测量弹性蛋白酶（NE）、髓过氧化物酶（MPO）、乳铁蛋白和基质金属蛋白酶-9（MMP-9）水平来评估中性粒细胞脱颗粒情况。通过基于Luminex的方法评估促炎细胞因子（IL-8、IL-1β、IL-6和TNF-α）和抗炎细胞因子（IL-4和IL-10）水平。
我们的结果表明，与对照组相比，NE（P = 0.015）、MPO（P = 0.042）、乳铁蛋白（P = 0.015）和MMP-9（P = 0.001）的释放显著增加。促炎细胞因子方面，IL-8显著升高（P = 0.019），IL-1β有升高趋势（P = 0.3196），IL-6无变化（P = 0.7329），TNF-α降低（P = 0.006）。抗炎细胞因子方面，IL-4升高（P = 0.057），IL-10降低（P = 0.05703）。
在生理缺氧条件下，AATD患者的中性粒细胞中观察到中性粒细胞脱颗粒增加和炎症表型。
