Impact of Hypoxia on Neutrophil Degranulation and Inflammatory Response in Alpha-1 Antitrypsin Deficiency Patients.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: Increased neutrophil degranulation and inflammatory phenotype are observed in AATD neutrophils under physiological hypoxia.