The effects of tumour necrosis factor alpha on mediator release from human lung

The effects of tumour necrosis factor alpha on mediator release from human lung
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DOI:
10.1006/pulp.1995.1004
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发表时间:
1995-02-01
期刊:
PULMONARY PHARMACOLOGY
影响因子:
--
通讯作者:
Armour, CL
Armour, CL
中科院分区:
其他
文献类型:
--
作者:
Hughes, JM;Stringer, RS;Armour, CL

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虽然肿瘤坏死因子α(TNF α)可能参与哮喘的病理过程,但其在人肺炎症细胞释放介质中的作用知之甚少。我们研究了TNF α是否诱导人切碎肺组织中肥大细胞释放组胺,以及它是否调节抗原诱导的被动致敏肺组织中组胺和白三烯C-4/D-4/E(4)的释放。在37 ℃下,在1 nM TNF α存在下持续4 h的自发组胺释放与单独的自发组胺释放无显著差异(4 h时分别为总组织组胺的6.1+/-1.3%和6.1+/-1.5%; n=3)。通过将屋尘螨屋尘螨在来自特应性志愿者供体的血清中在37 ℃下孵育3小时,使肺组织对屋尘螨屋尘螨被动致敏。在用低浓度(1.8 Au)D.屋尘螨引起抗原诱导的组胺释放量从总组织组胺的0.2+/-0.6%增加到1.9+/-1.0%(P=0.045,n=6)。TNF α处理对相同浓度抗原诱导的白三烯C-4/D-4/E(4)的释放没有显著影响(分别为39.5+/-9.1和55.6+/-17.7 pg/100 μ l上清液样品; n=6)。这些结果表明,TNF α可能参与过敏性哮喘中组胺释放的增强作用,特别是在低抗原浓度的情况下。
Although tumour necrosis factor alpha (TNF alpha) may be involved in the pathology of asthma, little is known about its role in mediator release from inflammatory cells in human lung. We investigated whether TNF alpha induced histamine release from mast cells in human chopped lung tissue and whether it modulated antigen-induced release of histamine and leukotrienes C-4/D-4/E(4) from passively sensitized lung tissue. Spontaneous histamine release in the presence of 1 nM TNF alpha for up to 4 h at 37 degrees C was not significantly different from spontaneous histamine release alone (6.1+/-1.3% and 6.1+/-1.5% of total tissue histamine at 4 h respectively; n=3). Lung tissue was passively sensitized to the house dust mite Dermatophagoides pteronyssinus by incubating it in serum from an atopic volunteer donor for 3 h at 37 degrees C. Treatment of the sensitized lung tissue with 1 nM TNF alpha for 60 min prior to challenge with a low concentration (1.8 AU) of D. pteronyssinus caused a significant increase in the amount of histamine release induced by the antigen from 0.2+/-0.6% to 1.9+/-1.0% of total tissue histamine (P=0.045, n=6). The release of leukotriene C-4/D-4/E(4) induced by the same concentration of antigen was not significantly changed by the TNF alpha treatment (39.5+/-9.1 and 55.6+/-17.7 pg/100 mu l supernatant sample respectively; n=6). These results suggest that TNF alpha may be involved in potentiation of histamine release in allergic asthma, particularly in the presence of low antigen concentrations.