Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, University of Leuven, 3000 Leuven, Belgium.
Pneumology and Cystic Fibrosis Unit, Department of Pneumology, University Hospitals Leuven, 3000 Leuven, Belgium.
Int J Mol Sci. 2021 Jun 8;22(12):6172. doi: 10.3390/ijms22126172.
The airways of patients with primary ciliary dyskinesia (PCD) contain persistently elevated neutrophil numbers and CXCL8 levels. Despite their abundance, neutrophils fail to clear the airways from bacterial infections. We investigated whether neutrophil functions are altered in patients with PCD. Neutrophils from patients and healthy controls (HC) were isolated from peripheral blood and exposed to various bacterial stimuli or cytokines. Neutrophils from patients with PCD were less responsive to low levels of fMLF in three different chemotaxis assays ( < 0.05), but expression of the fMLF receptors was unaltered. PCD neutrophils showed normal phagocytic function and expression of adhesion molecules. However, PCD neutrophils produced less reactive oxygen species upon stimulation with bacterial products or cytokines compared to HC neutrophils ( < 0.05). Finally, the capacity to release DNA, as observed during neutrophil extracellular trap formation, seemed to be reduced in patients with PCD compared to HC ( = 0.066). These results suggest that peripheral blood neutrophils from patients with PCD, in contrast to those of patients with cystic fibrosis or COPD, do not show features of over-activation, neither on baseline nor after stimulation. If these findings extend to lung-resident neutrophils, the reduced neutrophil activity could possibly contribute to the recurrent respiratory infections in patients with PCD.
原发性纤毛运动障碍（PCD）患者的气道中持续存在中性粒细胞数量和 CXCL8 水平升高。尽管数量丰富，但中性粒细胞未能清除气道中的细菌感染。我们研究了 PCD 患者的中性粒细胞功能是否发生改变。从患者和健康对照（HC）的外周血中分离中性粒细胞，并使其暴露于各种细菌刺激物或细胞因子中。在三种不同的趋化性测定中（<0.05），PCD 患者的中性粒细胞对低浓度 fMLF 的反应性降低，但 fMLF 受体的表达未改变。PCD 中性粒细胞表现出正常的吞噬功能和粘附分子表达。然而，与 HC 中性粒细胞相比，PCD 中性粒细胞在受到细菌产物或细胞因子刺激时产生的活性氧较少（<0.05）。最后，与 HC 相比，PCD 患者的中性粒细胞在形成中性粒细胞胞外诱捕网时释放 DNA 的能力似乎降低（=0.066）。这些结果表明，与囊性纤维化或 COPD 患者的中性粒细胞不同，PCD 患者的外周血中性粒细胞在基础状态或刺激后均未表现出过度激活的特征。如果这些发现扩展到肺驻留中性粒细胞，那么中性粒细胞活性的降低可能有助于 PCD 患者的反复呼吸道感染。
