Corticosteroid suppression of lipoxin A4 and leukotriene B4 from alveolar macrophages in severe asthma.
Corticosteroid suppression of lipoxin A4 and leukotriene B4 from alveolar macrophages in severe asthma.
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DOI：
10.1186/1465-9921-11-71
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发表时间：
2010-06-07
影响因子：
5.8
通讯作者：
Chung KF
中科院分区：
文献类型：
--
作者：
Bhavsar PK;Levy BD;Hew MJ;Pfeffer MA;Kazani S;Israel E;Chung KF
促炎性白三烯和反调节脂氧素的产生不平衡存在于严重哮喘中。我们测量了肺泡巨噬细胞（AM）产生的白三烯B4（LTB 4）和脂氧素A4（LXA 4），并研究了皮质类固醇的影响。用脂多糖（LPS，10 μg/ml）和地塞米松（10 ~（-6）M）刺激14例非哮喘患者、12例非重度哮喘患者和11例重度哮喘患者的AM。采用酶免疫分析法检测LTB 4和LXA 4。与非重度（p < 0.05）和正常受试者（p < 0.001）相比，重度哮喘AM的LXA 4生物合成减少。LPS诱导的LXA_4在正常人中最高，在重度哮喘患者中最低（P < 0.01）。与正常受试者相比，重度哮喘患者的LTB 4基础水平降低（p < 0.05），但与非重度哮喘患者相比则无差异。与非重度哮喘相比，重度哮喘中LPS诱导的LTB 4增加（p < 0.05）。地塞米松可抑制LPS诱导的LTB 4和LXA 4，重度哮喘患者对LTB 4的抑制程度较轻（p < 0.05）。LPS诱导的LXA 4与FEV 1（%预测值）之间存在显著相关性（rs = 0.60; p < 0.01）。LXA 4减少和LTB 4生成增加，加上LPS诱导的LTB 4而不是LXA 4的皮质类固醇敏感性受损，支持AM在重度哮喘中建立促炎平衡的作用。
An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene B4 (LTB4), and lipoxin A4 (LXA4) production by alveolar macrophages (AMs) and studied the impact of corticosteroids. AMs obtained by fiberoptic bronchoscopy from 14 non-asthmatics, 12 non-severe and 11 severe asthmatics were stimulated with lipopolysaccharide (LPS,10 μg/ml) with or without dexamethasone (10-6M). LTB4 and LXA4 were measured by enzyme immunoassay. LXA4 biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA4 induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTB4 were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTB4 was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTB4 and LXA4, with lesser suppression of LTB4 in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA4 and FEV1 (% predicted) (rs = 0.60; p < 0.01). Decreased LXA4 and increased LTB4 generation plus impaired corticosteroid sensitivity of LPS-induced LTB4 but not of LXA4 support a role for AMs in establishing a pro-inflammatory balance in severe asthma.
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影响因子：
4.4
作者：
Coffey, MJ;Phare, SM;Peters-Golden, M
通讯作者：
Peters-Golden, M
影响因子：
5.8
作者：
Bhavsar PK;Levy BD;Hew MJ;Pfeffer MA;Kazani S;Israel E;Chung KF
通讯作者：
Chung KF
影响因子：
4.8
作者：
Levy, Bruce D.;Lukacs, Nicholas W.;Parkinson, John F.
通讯作者：
Parkinson, John F.
影响因子：
82.9
作者：
Levy, BD;DeSanctis, GT;Serhan, CN
通讯作者：
Serhan, CN
DOI：
10.1124/jpet.300.3.868
发表时间：
2002-03-01
影响因子：
3.5
作者：
Profita, M;Sala, A;Vignola, AM
通讯作者：
Vignola, AM