Corrigan Chris, Mallett Kirsty, Ying Sun, Roberts David, Parikh Abhi, Scadding Glenis, Lee Tak
Department of Asthma, Allergy and Respiratory Science, Guy's Hospital, London, UK.
J Allergy Clin Immunol. 2005 Feb;115(2):316-22. doi: 10.1016/j.jaci.2004.10.051.
Cysteinyl leukotrienes play a disease-regulating role in rhinosinusitis and asthma, particularly aspirin-sensitive disease. They act through 2 G-protein coupled receptors termed cysteinyl leukotriene type 1 receptor (cysLT 1 ) and cysteinyl leukotriene type 2 receptor (cysLT 2 ). We previously compared expression of cysLT 1 on mucosal leukocytes in patients with aspirin-sensitive and aspirin-tolerant rhinosinusitis.
To compare expression of cysLT 1 and cysLT 2 on leukocytes, mucus glands, and epithelium in 32 patients with chronic polypoid rhinosinusitis (21 aspirin-sensitive, 11 aspirin-tolerant) and 9 normal controls.
Total numbers of CD45 + leukocytes, percentages of these cells expressing cysLT 1 or cysLT 2 , and percentages of the total epithelial and glandular areas expressing cysLT 1 or cysLT 2 were measured in sections of nasal biopsies by using immunohistochemistry and image analysis.
The percentages of mucosal CD45 + leukocytes expressing cysLT 1 were significantly ( P < .0001) elevated in the aspirin-sensitive but not the aspirin-tolerant patients compared with the controls. In contrast, the percentages of leukocytes expressing cysLT 2 did not differ significantly in the 3 groups. On epithelial and glandular cells, expression of cysLT 2 significantly exceeded that of cysLT 1 in both the patients with rhinosinusitis and the controls ( P < or = .004), although there was no significant difference in the expression of either receptor in the patients with rhinosinusitis (aspirin-sensitive or aspirin-tolerant) and the controls.
Although cysLT 1 expression predominates on inflammatory leukocytes in patients with aspirin-sensitive rhinosinusitis, the effects of cysteinyl leukotrienes on glands and epithelium may be mediated predominantly through cysLT 2. This has potentially important therapeutic implications.
半胱氨酰白三烯在鼻窦炎和哮喘,尤其是阿司匹林敏感性疾病中发挥疾病调节作用。它们通过两种G蛋白偶联受体发挥作用,这两种受体分别称为半胱氨酰白三烯1型受体(cysLT1)和半胱氨酰白三烯2型受体(cysLT2)。我们之前比较了阿司匹林敏感性和阿司匹林耐受性鼻窦炎患者黏膜白细胞上cysLT1的表达。
比较32例慢性息肉样鼻窦炎患者(21例阿司匹林敏感,11例阿司匹林耐受)和9例正常对照者白细胞、黏液腺及上皮细胞上cysLT1和cysLT2的表达。
采用免疫组化和图像分析方法,在鼻活检切片中测量CD45+白细胞总数、表达cysLT1或cysLT2的这些细胞的百分比,以及表达cysLT1或cysLT2的上皮和腺体总面积的百分比。
与对照组相比,阿司匹林敏感患者而非阿司匹林耐受患者中,表达cysLT1的黏膜CD45+白细胞百分比显著升高(P<.0001)。相比之下,3组中表达cysLT2的白细胞百分比无显著差异。在鼻窦炎患者和对照组的上皮及腺细胞上,cysLT2的表达均显著超过cysLT1(P≤.004),尽管鼻窦炎患者(阿司匹林敏感或阿司匹林耐受)与对照组中任一受体的表达均无显著差异。
尽管在阿司匹林敏感性鼻窦炎患者中,cysLT1表达在炎性白细胞上占主导,但半胱氨酰白三烯对腺体和上皮的作用可能主要通过cysLT2介导。这具有潜在的重要治疗意义。