Xaubet A, Mullol J, López E, Roca-Ferrer J, Rozman M, Carrión T, Fabra J M, Picado C
Serveis de Pneumologia i Hematologia, Hospital Clinic, Barcelona, Catalonia, Spain.
Clin Exp Allergy. 1994 Apr;24(4):307-17. doi: 10.1111/j.1365-2222.1994.tb00240.x.
Eosinophilic infiltration of the respiratory mucosa is considered an inflammatory hallmark of allergic rhinitis, bronchial asthma and nasal polyposis. However, the mechanisms involved in this infiltration have not yet been totally elucidated. The objective of this study was to investigate and compare the influence of epithelial cell secretions from both nasal polyps (NP) and normal nasal mucosa (NM) on in vitro eosinophil survival. Epithelial cells were identified by microscopy and immunohistochemistry, cultured to confluence, and human epithelial cell conditioned media (HECM) was generated from cultures. Eosinophils were isolated at high viability and purity (> 90%) from peripheral blood and incubated with HECM. HECM from both NM and NP increased eosinophil survival in a dose-dependent manner, this effect being maximal at a concentration of 25% for NM (73.4% +/- 5.5%, n = 26, P < 0.001) and of 10% for NP (74.5% +/- 8.4%, n = 18, P < 0.001). Incubation of monoclonal antibody to human GM-CSF with HECM, neutralized the induction of eosinophil survival by HECM from both NM and NP. HECM from NP contained higher concentrations of GM-CSF (111 +/- 25.4 pg/ml, n = 17) than HECM from NM (97.1 +/- 15.2 pg/ml, n = 8), without reaching statistical significance. Pre-incubation of dexamethasone with eosinophils also blocked HECM-induced eosinophil survival from both NM (10(-8)-10(-5) M; IC50 = 9.5 nM) and NP (10(-7)-10(-5) M; IC50 = 83 nM). These results suggest that: firstly eosinophil infiltration into the respiratory mucosa during allergic reaction and nasal polyposis may be modulated at least in part by GM-CSF from epithelial cells; and secondly epithelial cells from NP might have a more potent effect on inducing eosinophil infiltration of the respiratory mucosa than epithelial cells from NM. Finally, we may consider this as a reliable in vitro model to compare the role of epithelial cells from inflammatory (NP) and non-inflammatory (NM) tissue in respiratory inflammation.
呼吸道黏膜的嗜酸性粒细胞浸润被认为是变应性鼻炎、支气管哮喘和鼻息肉的炎症标志。然而，这种浸润所涉及的机制尚未完全阐明。本研究的目的是调查和比较鼻息肉（NP）和正常鼻黏膜（NM）的上皮细胞分泌物对体外嗜酸性粒细胞存活的影响。通过显微镜检查和免疫组织化学鉴定上皮细胞，培养至汇合状态，并从培养物中生成人上皮细胞条件培养基（HECM）。从外周血中以高活力和纯度（>90%）分离嗜酸性粒细胞，并与HECM孵育。来自NM和NP的HECM均以剂量依赖方式增加嗜酸性粒细胞的存活，这种效应在NM浓度为25%（73.4%±5.5%，n = 26，P < 0.001）和NP浓度为10%（74.5%±8.4%，n = 18，P < 0.001）时达到最大。将抗人GM-CSF单克隆抗体与HECM一起孵育，可中和来自NM和NP的HECM对嗜酸性粒细胞存活的诱导作用。来自NP的HECM中GM-CSF的浓度（111±25.4 pg/ml，n = 17）高于来自NM的HECM（97.1±15.2 pg/ml，n = 8），但未达到统计学意义。地塞米松与嗜酸性粒细胞预孵育也可阻断来自NM（10^(-8)-10^(-5) M；IC50 = 9.5 nM）和NP（10^(-7)-10^(-5) M；IC50 = 83 nM）的HECM诱导的嗜酸性粒细胞存活。这些结果表明：首先，变应性反应和鼻息肉形成过程中嗜酸性粒细胞向呼吸道黏膜的浸润可能至少部分受上皮细胞来源的GM-CSF调节；其次，NP的上皮细胞可能比NM的上皮细胞对诱导呼吸道黏膜嗜酸性粒细胞浸润具有更强的作用。最后，我们可以将此视为一种可靠的体外模型，用于比较炎症（NP）和非炎症（NM）组织的上皮细胞在呼吸道炎症中的作用。
