Tomee J F, van Weissenbruch R, de Monchy J G, Kauffman H F
Department of Allergology, University Hospital Groningen, The Netherlands.
J Allergy Clin Immunol. 1998 Jul;102(1):75-85. doi: 10.1016/s0091-6749(98)70057-0.
The factors responsible for inducing or maintaining airway inflammation are poorly understood. Various studies have focussed on the mechanisms leading to allergic airway inflammation in patients with asthma and rhinitis. The observation of local airway inflammation in nonallergic patients with asthma or rhinitis, including those with nasal polyposis, suggest that non-IgE-related mechanisms exist that may lead to airway inflammation. Various lines of evidence suggest that epithelial cells may participate in local inflammation of the airways.
This study focused on the interaction of airway epithelial cells with clinically relevant inhalant allergen extracts in vitro.
Cultures of airway epithelial cells were exposed to mite, Timothy grass pollen, and birch pollen extracts. Production of IL-8, IL-6, monocyte-chemotactic protein-1 (MCP-1), and granulocyte-macrophage colony-stimulating factor and cell detachment were monitored while protease inhibitors and chromatography techniques were applied to identify the factors responsible for these effects.
With the mite extracts, cytokine production and cell detachment was largely dependent on protease activity. With the pollen extracts, cytokine production without cell detachment seemed to be independent of protease activity.
These findings support the view that epithelial cells may contribute to the pathogenesis of airway disease by their interaction with inhalant allergen extracts. Furthermore, allergen extracts may enhance airway inflammation by means other than their IgE-binding activity through both protease-dependent and protease-independent mechanisms.
导致或维持气道炎症的因素尚不清楚。各种研究都集中在哮喘和鼻炎患者中导致过敏性气道炎症的机制上。对非过敏性哮喘或鼻炎患者(包括鼻息肉患者)局部气道炎症的观察表明,存在可能导致气道炎症的非IgE相关机制。各种证据表明,上皮细胞可能参与气道的局部炎症。
本研究聚焦于气道上皮细胞与临床相关吸入性变应原提取物在体外的相互作用。
将气道上皮细胞培养物暴露于螨、梯牧草花粉和桦树花粉提取物中。监测白细胞介素-8(IL-8)、白细胞介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)、粒细胞-巨噬细胞集落刺激因子的产生以及细胞脱离情况,同时应用蛋白酶抑制剂和色谱技术来确定造成这些影响的因素。
对于螨提取物,细胞因子的产生和细胞脱离在很大程度上依赖于蛋白酶活性。对于花粉提取物,不伴有细胞脱离的细胞因子产生似乎与蛋白酶活性无关。
这些发现支持这样一种观点,即上皮细胞可能通过与吸入性变应原提取物相互作用而参与气道疾病的发病机制。此外,变应原提取物可能通过蛋白酶依赖性和蛋白酶非依赖性机制,以其IgE结合活性以外的方式增强气道炎症。