Simpson Jodie L, Gibson Peter G, Yang Ian A, Upham John, James Alan, Reynolds Paul N, Hodge Sandra
Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia.
Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
Respirology. 2014 Feb;19(2):280-287. doi: 10.1111/resp.12213. Epub 2013 Dec 23.
The non-eosinophilic phenotype of asthma (NEA) is associated with chronic airway inflammation and airway neutrophilia. An accumulation of apoptotic airway epithelial cells, if not efficiently cleared by efferocytosis, can undergo secondary necrosis, with the potential for inflammation of surrounding tissues. Apoptosis may occur via the T cell granzyme B pathway. The role of granzyme B in NEA is not known. The aim of this study was to investigate production of granzyme B and its inhibitor proteinase inhibitor (PI)-9 by T cells from induced sputum and compare expression between eosinophilic, NEA and healthy controls.
We investigated T cell intracellular granzyme B and its inhibitor, PI-9, in sputum from healthy control subjects (n = 10), and patients with NEA (n = 22) or eosinophilic asthma (EA) (n = 15) using flow cytometry.
Granzyme B expression and the ratio of granzyme B to PI-9 positive cells were highest in those with NEA for both CD3+ and CD4+ T cells. The expression of granzyme B was not statistically different between patients with NEA and EA; however, the ratio of granzyme B to PI-9 positive cells for CD3+ T cells was significantly higher in those with NEA compared with EA.
Induced sputum provides a non-invasive tool for investigating T cell cytotoxic mediators in the various asthma subtypes. Granzyme B expression is increased in NEA and the contribution of granzyme B to chronic inflammation requires further study.
哮喘的非嗜酸性粒细胞表型（NEA）与慢性气道炎症和气道嗜中性粒细胞增多有关。凋亡的气道上皮细胞若未被胞葬作用有效清除，可能会发生继发性坏死，进而引发周围组织炎症。细胞凋亡可能通过T细胞颗粒酶B途径发生。颗粒酶B在NEA中的作用尚不清楚。本研究旨在调查诱导痰中T细胞产生颗粒酶B及其抑制蛋白蛋白酶抑制剂（PI）-9的情况，并比较嗜酸性粒细胞性哮喘、NEA和健康对照之间的表达差异。
我们使用流式细胞术研究了健康对照者（n = 10）、NEA患者（n = 22）或嗜酸性粒细胞性哮喘（EA）患者（n = 15）痰液中的T细胞内颗粒酶B及其抑制剂PI-9。
对于CD3+和CD4+ T细胞，NEA患者的颗粒酶B表达以及颗粒酶B与PI-9阳性细胞的比例最高。NEA患者和EA患者之间颗粒酶B的表达无统计学差异；然而，与EA患者相比，NEA患者CD3+ T细胞的颗粒酶B与PI-9阳性细胞的比例显著更高。
诱导痰为研究不同哮喘亚型中的T细胞细胞毒性介质提供了一种非侵入性工具。NEA中颗粒酶B的表达增加，颗粒酶B对慢性炎症的作用需要进一步研究。
