Asthma and endotoxin: Lipopolysaccharide-binding protein and soluble CD14 in bronchoalveolar compartment
Asthma and endotoxin: Lipopolysaccharide-binding protein and soluble CD14 in bronchoalveolar compartment
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DOI：
10.1152/ajplung.1996.270.5.l736
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发表时间：
1996-05-01
影响因子：
4.9
通讯作者：
Hasday, JD
中科院分区：
文献类型：
--
作者：
Dubin, W;Martin, TR;Hasday, JD
在过敏性哮喘中，吸入抗原引起早期微血管通透性增加，伴有蛋白质外渗和炎性细胞延迟募集。我们发现12名无哮喘受试者（86.5 +/- 53.8 pg/ml）和12名轻度哮喘受试者（111 +/- 37.0 pg/ml）的支气管肺泡灌洗液（BALF）中存在相似浓度的脂多糖（LPS）。这些LPS水平在没有辅助分子的情况下不足以刺激细胞因子释放。在11例对豚草过敏的哮喘患者中，肺段性豚草抗原激发后24小时的BALF中，与抗原前BALF相比，两种LPS辅助分子的水平增加，LPS结合蛋白（LBP）增加158倍。（4.83 +/- 2.02 vs. 742 +/- 387 ng/ml; P < 0.03）和31.6倍的可溶性CD 14（sCD 14）（3.45 +/- 1.04 vs. 110 +/- 51.6 ng/ml; P < 0.02）。Postantigen BALF增强了荧光素结合的LPS与CD 14-轴承THP-1细胞的结合，并支持LPS诱导的非CD 14-轴承内皮细胞表达细胞间粘附分子-1和白细胞介素-6，表明功能性LBP和sCD 14。我们认为，LBP和sCD 14外渗到支气管肺泡隔室吸入抗原后，可能会增加吸入或吸出的LPS激活炎症级联反应，可能会放大某些哮喘患者吸入抗原的炎症反应的能力。
In allergic asthma, inhalation of antigen provokes an early increase in microvascular permeability with protein extravasation and a delayed recruitment of inflammatory cells. We showed that similar concentrations of lipopolysaccharide (LPS) are present in bronchoalveolar lavage fluid (BALF) in 12 subjects without asthma (86.5 +/- 53.8 pg/ml) and 12 subjects with mild asthma (111 +/- 37.0 pg/ml). These LPS levels are insufficient to stimulate cytokine release without accessory molecules. BALF obtained 24 h after segmental ragweed antigen challenge in 11 asthmatics allergic to ragweed contained increased levels of two LPS accessory molecules compared with preantigen BALF, 158-fold more LPS-binding protein (LBP) (4.83 +/- 2.02 vs. 742 +/- 387 ng/ml; P < 0.03) and 31.6-fold more soluble CD14 (sCD14) (3.45 +/- 1.04 vs. 110 +/- 51.6 ng/ml; P < 0.02). Postantigen BALF enhanced binding of fluorescein-conjugated LPS to CD14-bearing THP-1 cells and supported LPS-induced non-CD14-bearing endothelial cell expression of intercellular adhesion molecule-1 and interleukin-6, indicating functional LBP and sCD14. We suggest that extravasation of LBP and sCD14 into the bronchoalveolar compartment after antigen inhalation may enhance the capacity of inhaled or aspirated LPS to activate an inflammatory cascade that may amplify the inflammatory response to inhaled antigen in some asthmatics.