Role of 1ymphocytes in airway inflammation and hyperresponsiveness induced by diesel exhaust particles.

以往的实验研究表明，鼻腔滴注柴油机尾气微粒(DEP)可以增强鼻腔LGE反应和细胞因子的产生；然而，没有实验证据表明DEP与过敏性哮喘之间的关系。我们研究了DEP气管内接种对抗原诱导的小鼠呼吸道炎症、细胞因子蛋白的局部表达和抗原特异性免疫球蛋白产生的影响。DEP加重卵清蛋白诱导的气道炎症，其特征是嗜酸性粒细胞和淋巴细胞的浸润以及支气管上皮中杯状细胞的增加。有抗原的DEP可显著提高白细胞介素值。肺组织和支气管肺泡灌洗上清液中5(IL-5)蛋白水平与抗原或DEP单独比较。联合应用DEP和抗原后，局部IL-4、GM-CSF和IL-2的表达显著增加，而干扰素-γ的表达无明显变化。此外，DEP还显示了抗原特异性产生IgG和IgE的佐剂活性。这些结果首次提供了DEP可以增强过敏性哮喘表现的实验证据。这种增强可能主要通过IL-5局部表达的增加以及IL-4、GM-CSF和IL-2的调节表达来实现。

Previous experimental studies have suggested that nasal instillation of diesel exhaust particles (DEP) can enhance nasal lgE response and cytokine production ; However, there is no experimental evidence for the relation of DEP to allergic asthma. We investigated the effects of DEP inoculated intratracheally on antigen-induced airway inflammation, local expression of cytokine proteins, and antigen-specific immunoglobulin production in mice. DEP aggravated ovalbumin-induced airway inflammation characterized by infiltration of eosinophils and lymphocytes and an increase in goblet cells in bronchial epithelium. DEP with antigen markedly increased interleukin. 5 (lL-5) protein levels in lung tissue and bronchoalveolar lavage supernatants compared with either antigen or DEP alone. The combination of DEP and antigen induced significant increases in local expression of IL-4, granulocyte macrophage-colony stimulating factor (GM-CSF), and IL-2, whereas expression of interferon-gamma was not affected. In addition, DEP exhibited adjuvant activity for the antigen-specific production of lgG and lgE.These results provide the first experimental evidence that DEP can enhance the manifestations of allergic asthma. The enhancement may be mediated mainly by the increased local expression of IL-5, and also by the modulated expression of lL-4, GM-CSF,and lL-2.