Bayram H, Devalia J L, Khair O A, Abdelaziz M M, Sapsford R J, Sagai M, Davies R J
Academic Department of Respiratory Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, The London Chest Hospital, London E2 9JX, UK.
J Allergy Clin Immunol. 1998 Nov;102(5):771-82. doi: 10.1016/s0091-6749(98)70017-x.
Recent studies have suggested that asthmatic patients may be more susceptible to the adverse effects of air pollutants, including diesel exhaust particles (DEP). The underlying mechanisms, however, are not clear.
We cultured bronchial epithelial cells from bronchial biopsy specimens of well-characterized groups of nonatopic, nonasthmatic individuals and atopic patients with mild asthma and compared the ciliary beat frequency (CBF) and release of IL-8, GM-CSF, regulated on activation, normal T-cell expressed and secreted (RANTES), and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells both before and after exposure for 24 hours to 10 to 100 micrograms/mL DEP in vitro.
The baseline CBF was not found to be significantly different in the bronchial epithelial cell cultures of nonasthmatic and asthmatic individuals. Incubation with DEP significantly attenuated the CBF of both the nonasthmatic and asthmatic bronchial epithelial cell cultures at all concentrations of DEP investigated and were maximal (55.5% and 45.2%, respectively) after incubation with 100 micrograms/mL DEP. The bronchial epithelial cell cultures of asthmatic patients constitutively released significantly greater amounts of IL-8, GM-CSF, and sICAM-1 than bronchial epithelial cell cultures of nonasthmatic subjects. The cultures of only asthmatic patients additionally released RANTES. Incubation of the asthmatic cultures with 10 micrograms/mL DEP significantly increased the release of IL-8 (from 102.0 to 167.8 pg/micrograms cellular protein; P <.01), GM-CSF (from 0.43 to 1.87 pg/micrograms cellular protein; P <.01), and sICAM-1 (from 14.7 to 38.1 pg/micrograms cellular protein; P <.02) after 24 hours. Incubation with 50 to 100 micrograms/mL DEP, however, significantly decreased the release of IL-8 and RANTES from these cultures. In contrast, only the higher concentrations of 50 to 100 micrograms/mL DEP significantly increased release of IL-8 (from 37.9 to 71.5 pg/micrograms cellular protein; P <.05) and GM-CSF (from 0.06 to 0. 34 pg/micrograms cellular protein; P <.05) from the bronchial epithelial cells of nonasthmatic individuals.
These results suggest that bronchial epithelial cells of asthmatic subjects are different from bronchial epithelial cells of nonasthmatic subjects with regard to the amounts and types of proinflammatory mediators they can release and that the increased sensitivity of bronchial epithelial cells of asthmatic subjects to DEP may possibly result in exacerbation of their disease symptoms.
最近的研究表明，哮喘患者可能更容易受到空气污染物的不良影响，包括柴油废气颗粒（DEP）。然而，其潜在机制尚不清楚。
我们从非特应性、非哮喘个体以及轻度哮喘特应性患者的支气管活检标本中培养支气管上皮细胞，并比较了这些细胞在体外暴露于10至100微克/毫升DEP 24小时前后的纤毛摆动频率（CBF）以及白细胞介素-8（IL-8）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、活化调节正常T细胞表达和分泌因子（RANTES）和可溶性细胞间黏附分子-1（sICAM-1）的释放情况。
在非哮喘和哮喘个体的支气管上皮细胞培养物中，未发现基线CBF有显著差异。在所有研究的DEP浓度下，与DEP孵育均显著减弱了非哮喘和哮喘支气管上皮细胞培养物的CBF，在与100微克/毫升DEP孵育后达到最大值（分别为55.5%和45.2%）。哮喘患者的支气管上皮细胞培养物中IL-8、GM-CSF和sICAM-1的组成性释放量显著高于非哮喘受试者的支气管上皮细胞培养物。只有哮喘患者的培养物还释放RANTES。哮喘培养物与10微克/毫升DEP孵育24小时后，IL-8（从102.0皮克/微克细胞蛋白增加到167.8皮克/微克细胞蛋白；P<.01）、GM-CSF（从0.43皮克/微克细胞蛋白增加到1.87皮克/微克细胞蛋白；P<.01）和sICAM-1（从14.7皮克/微克细胞蛋白增加到38.1皮克/微克细胞蛋白；P<.02）的释放显著增加。然而，与50至100微克/毫升DEP孵育显著降低了这些培养物中IL-8和RANTES的释放。相比之下，只有50至100微克/毫升的较高浓度DEP显著增加了非哮喘个体支气管上皮细胞中IL-8（从37.9皮克/微克细胞蛋白增加到71.5皮克/微克细胞蛋白；P<.05）和GM-CSF（从0.06皮克/微克细胞蛋白增加到0.34皮克/微克细胞蛋白；P<.05）的释放。
这些结果表明，哮喘受试者的支气管上皮细胞在可释放的促炎介质的数量和类型方面与非哮喘受试者的支气管上皮细胞不同，并且哮喘受试者支气管上皮细胞对DEP的敏感性增加可能会导致其疾病症状加重。
