背景:嗜酸性粒细胞与肥大细胞(MC)之间的双向相互作用已在各种过敏性疾病中得到报道。骨髓(BM)嗜酸性粒细胞增多,血液嗜酸性粒细胞增多程度较低,常见于系统性肥大细胞增多症(SM),但它的意义仍然未知。
目的:描述SM的血液和BM嗜酸性粒细胞特征。
方法:使用免疫组织化学染色和全载玻片成像分析大量BM活检。嗜酸性粒细胞过氧化物酶(EPX)染色检测嗜酸性粒细胞和细胞外颗粒,和MC通过KIT染色。使用流式细胞术和免疫荧光进行补充分析。
结果:在SM的BMMC浸润内或周围观察到嗜酸性粒细胞浸润和大面积的嗜酸性粒细胞脱颗粒。EPX染色表面,突出完整的嗜酸性粒细胞和嗜酸性粒细胞脱颗粒,与两个对照(n=8,p=0.0003)和高级SM(n=24,p=0.014)相比,非高级SM(n=37BM活检)均较高。在非高级SM中,血清类胰蛋白酶水平与BM期望中嗜酸性粒细胞计数百分比之间存在正相关(Spearmanr系数r=0.38,p=0.038),BM活检中的嗜酸性粒细胞计数(r=0.45,p=0.007),EPX染色(r=0.37,p=0.035)和嗜酸性粒细胞脱颗粒(r=0.39,p=0.023)。BM活检中的嗜酸性粒细胞计数也与MC计数(r=0.47,p=0.006)和KIT染色表面(r=0.49,p=0.003)相关。BMMC表达白细胞介素-5受体和其他常见的嗜酸性粒细胞细胞因子/趋化因子受体,与对照组相比,血液嗜酸性粒细胞显示出几种增加的表面标志物,建议一个激活状态。
结论:我们的数据表明MC和嗜酸性粒细胞之间可能存在串扰,支持MC类胰蛋白酶释放和MC激活相关症状。这表明在未被其他疗法完全控制的非晚期SM中靶向嗜酸性粒细胞的理由。
BACKGROUND: Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown.
OBJECTIVE: To describe blood and BM eosinophil characteristics in SM.
METHODS: A large collection of BM biopsies was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining, and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence.
RESULTS: Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in non-advanced-SM (n=37 BM biopsies) compared to both controls (n=8, p=0.0003) and to advanced SM (n=24, p=0.014). In non-advanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r=0.38, p=0.038), eosinophils count in BM biopsies (r=0.45, p=0.007), EPX staining (r=0.37, p=0.035) and eosinophil degranulation (r=0.39, p=0.023). Eosinophil counts in BM biopsies also correlated with MC counts (r=0.47, p=0.006) and KIT staining surface (r=0.49, p=0.003). BM MCs expressed interleukin-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils display several increased surface markers compared to controls, suggesting an activated state.
CONCLUSIONS: Our data suggest a possible crosstalk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in non-advanced-SM not fully controlled by other therapies.