Al-Rashoudi Reem, Moir Gillian, Al-Hajjaj Mohamed S, Al-Alwan Monther M, Wilson Heather M, Crane Isabel J
1School of Medicine, Medical Sciences and Nutrition, University of Aberdeen Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD Scotland, UK.
2Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
Allergy Asthma Clin Immunol. 2019 Nov 4;15:64. doi: 10.1186/s13223-019-0379-5. eCollection 2019.
Monocytes play an important role in immune and inflammatory diseases and monocyte subsets are predictors of disease in certain conditions. Expression of the chemokine receptors, CCR2 and CXCR1 on monocyte subsets relates to their function and can be used in their characterization. Our objective was to determine whether CD14, CD16, CCR2 and CXCR1 on monocyte subsets are potential indicators of asthma severity.
Blood samples were collected from Saudi Arabian patients with asthma and normal healthy individuals. Six-color flow-cytometry phenotypic analysis was used to identify human blood monocyte subsets, based on their expression of CD14 and CD16 following CD45 gating. Expression of CCR2 and CXCR1 was analysed on classical (CD14CD16), intermediate (CD14CD16) and non-classical (CD14CD16) subsets and correlated with disease severity.
We demonstrated a significant increase in percentage of total CD45-positive monocytes in the blood of patients with severe asthma, but the proportion of the individual monocyte subsets was not significantly changed when patients with mild, moderate and severe asthma were compared with healthy individuals. CD16 expression (mean fluorescence intensity, MFI) was decreased on intermediate and non-classical subsets in patients with severe asthma compared to healthy controls. CXCR1 expression was also lower, with a lower percentage of cells expressing CXCR1 in the non-classical CD14CD16 subset in all patients with asthma and this was inversely related to the percentage of cells expressing CCR2.
CCR2 expression on monocytes indicated a tendency toward more phagocytic monocytes in patients with asthma. The differential expression of CD16, CXCR1 and CCR2 on monocyte subsets in peripheral blood indicates modulation of the inflammatory response and suggests a role for monocytes in asthma pathogenesis.
单核细胞在免疫和炎症性疾病中发挥重要作用,在某些情况下单核细胞亚群是疾病的预测指标。趋化因子受体CCR2和CXCR1在单核细胞亚群上的表达与其功能相关,可用于其特征描述。我们的目的是确定单核细胞亚群上的CD14、CD16、CCR2和CXCR1是否为哮喘严重程度的潜在指标。
采集沙特阿拉伯哮喘患者和正常健康个体的血样。基于CD45门控后CD14和CD16的表达,采用六色流式细胞术表型分析来鉴定人血单核细胞亚群。分析经典(CD14⁺CD16⁻)、中间(CD14⁺CD16⁺)和非经典(CD14⁻CD16⁺)亚群上CCR2和CXCR1的表达,并与疾病严重程度相关联。
我们发现重度哮喘患者血液中总CD45阳性单核细胞百分比显著增加,但与健康个体相比,轻度、中度和重度哮喘患者的单个单核细胞亚群比例无显著变化。与健康对照相比,重度哮喘患者中间和非经典亚群上的CD16表达(平均荧光强度,MFI)降低。CXCR1表达也较低,所有哮喘患者非经典CD14⁻CD16⁺亚群中表达CXCR1的细胞百分比更低,且这与表达CCR2的细胞百分比呈负相关。
单核细胞上CCR2的表达表明哮喘患者中单核细胞有更强的吞噬倾向。外周血单核细胞亚群上CD16、CXCR1和CCR2的差异表达表明炎症反应受到调节,并提示单核细胞在哮喘发病机制中发挥作用。