Lemiere C, Pelissier S, Tremblay C, Chaboillez S, Thivierge M, Stankova J, Rola-Pleszczynski M
Department of Chest Medicine, Hôpital du Sacré-Coeur, Montreal, University of Montreal, QC, Canada.
Clin Exp Allergy. 2004 Nov;34(11):1684-9. doi: 10.1111/j.1365-2222.2004.02102.x.
The role of leukotrienes (LTs) in the pathophysiology of isocyanate-induced asthma is not well known.
We sought to characterize the type of airway inflammation induced by exposure to isocyanates and to investigate whether exposure to isocyanates induced an increase in LT receptor cysteinyl leukotriene ((CysLT)(1), CysLT(2) and leukotriene B(4) receptor (BLT(1))) expression, as well as a release of LT (LTC(4) and leukotriene B(4) (LTB(4))) and IL-8 in both asthmatics with isocyanate-induced asthma and healthy subjects.
We investigated eight subjects with isocyanate-induced asthma and eight healthy subjects. Both groups underwent specific inhalation challenges to isocyanates in the laboratory. Induced sputum was collected before and after exposure to isocyanates. CysLT(1), CysLT(2) and BLT(1) expression was assessed by flow cytometry, whereas LTC(4), LTB(4) and IL-8 were measured in the sputum supernatants by enzyme immunoassay.
Exposure to isocyanates induced an increase in sputum neutrophils only in subjects with occupational asthma. There was a significant increase in CysLT(1) and BLT(1) receptor expression, as well as a release of LTB(4) and IL-8 after exposure to isocyanates compared with the baseline, only in subjects with isocyanate-induced asthma, whereas there was no increase in LTC(4). Exposure to isocyanates did not induce any change in LT receptor expression nor in the levels of LTC(4), LTB(4) and IL-8, in healthy subjects.
The neutrophilia observed after exposure to isocyanates is likely to be related to the release of LTB(4), probably enhanced by the increased expression of BLT(1) on neutrophils as well as by the release of IL-8. The significance of the increase of CysLT1 receptor expression on neutrophils is unknown and needs further investigation.
白三烯（LTs）在异氰酸酯诱发哮喘的病理生理学中的作用尚不清楚。
我们试图明确接触异氰酸酯所诱发的气道炎症类型，并研究接触异氰酸酯是否会导致异氰酸酯诱发哮喘的哮喘患者及健康受试者体内白三烯受体半胱氨酰白三烯（（CysLT）（1）、CysLT（2）和白三烯B4受体（BLT（1）））表达增加，以及白三烯（LTC（4）和白三烯B4（LTB（4）））和白细胞介素-8的释放情况。
我们研究了8名异氰酸酯诱发哮喘的受试者和8名健康受试者。两组均在实验室中接受了针对异氰酸酯的特异性吸入激发试验。在接触异氰酸酯前后收集诱导痰。通过流式细胞术评估CysLT（1）、CysLT（2）和BLT（1）的表达，而痰上清液中的LTC（4）、LTB（4）和白细胞介素-8则通过酶免疫测定法进行检测。
仅在职业性哮喘患者中，接触异氰酸酯会导致痰中中性粒细胞增多。与基线相比，仅在异氰酸酯诱发哮喘的患者中，接触异氰酸酯后CysLT（1）和BLT（1）受体表达显著增加，以及LTB（4）和白细胞介素-8释放，而LTC（4）没有增加。在健康受试者中，接触异氰酸酯未引起LT受体表达以及LTC（4）、LTB（4）和白细胞介素-8水平的任何变化。
接触异氰酸酯后观察到的中性粒细胞增多可能与LTB（4）的释放有关，可能是由于中性粒细胞上BLT（1）表达增加以及白细胞介素-8的释放而增强。中性粒细胞上CysLT1受体表达增加的意义尚不清楚，需要进一步研究。
