Interleukin-4 and lipopolysaccharide synergize to induce vascular cell adhesion molecule-1 expression in human lung microvascular endothelial cells
Interleukin-4 and lipopolysaccharide synergize to induce vascular cell adhesion molecule-1 expression in human lung microvascular endothelial cells
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DOI：
10.1165/ajrcmb.18.5.3052
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发表时间：
1998-05-01
影响因子：
6.4
通讯作者：
Burke-Gaffney, A
中科院分区：
文献类型：
--
作者：
Blease, K;Seybold, J;Burke-Gaffney, A
最近的研究表明，血管细胞粘附分子-1（VCAM-1）在支气管粘膜活检血管内皮细胞上的表达增加与过敏性哮喘患者细支气管灌洗液中的白细胞介素-4（IL-4）水平相关。对屋尘螨过敏的患者的哮喘严重程度也被证明与脂多糖（LPS）相关。而不是过敏原，集中在灰尘中。我们假设，为了诱导人肺微血管内皮细胞（HLM-VEC）中有效的VCAM-1表达，IL-4可能需要存在共刺激物如LPS。为了验证这一假设，我们测量，通过酶联免疫吸附试验，诱导细胞粘附分子的表达，和人嗜酸性粒细胞粘附，培养的HLMVEC单层预处理与IL-4单独或与LPS结合。IL-4与LPS协同诱导VCAM-1在24、48或72 h表达，而单独IL-4仅在72 h诱导表达。IL-4不诱导细胞间粘附分子-1或E-选择素的表达或改变LPS诱导的表达。HLMVEC预暴露于LPS或IL-4（1 h），随后分别暴露于IL-4或LPS（23 h），也诱导VCAM-1表达。用IL-4和LPS共同处理（但单独处理）的HLMVEC单层上的嗜酸性粒细胞粘附显着（P < 0.001）从9.6 +/- 1.5%（对照）增加到26.9 +/- 3.3%，并且被抗VCAM的单克隆抗体抑制-1配体，非常晚期抗原-4。VCAM-1 mRNA的分析揭示了IL-4和LPS之间的协同作用，这可能部分有助于增强VCAM-1表达。这些结果表明，共刺激物如LPS的存在可能是IL-4有效诱导肺微血管中VCAM-1表达所必需的。
Recent studies suggest that increased vascular cell adhesion molecule-1 (VCAM-1) expression on vascular endothelium in bronchial mucosa biopsies correlates with interleukin-4 (IL-4) levels in bronchiolar lavage fluid of allergic asthmatics. The severity of asthma in patients allergic to house dust mite has also been shown to correlate with lipopolysaccharide (LPS). rather than allergen, concentration in dust. We hypothesized that to induce effective VCAM-1 expression in human lung microvascular endothelial cells (HLM-VEC), IL-4 may require the presence of a co-stimulus such as LPS. To test this hypothesis we measured, by enzyme-linked immunosorbent assay, induction of cell adhesion molecule expression on, and human eosinophil adhesion to, cultured HLMVEC monolayers pretreated with IL-4 alone or combined with LPS. IL-4 synergized with LPS to induce VCAM-1 expression at 24, 48, or 72 h, whereas IL-4 alone induced expression at 72 h only. IL-4 did not induce expression of intercellular adhesion molecule-1 or E-selectin or alter LPS-induced expression of either. Pre-exposure of HLMVEC to LPS or IL-4 (1 h), followed by IL-4 or LPS, respectively (23 h), also induced VCAM-1 expression. Eosinophil adhesion to HLMVEC monolayers treated with IL-4 and LPS together, but not alone, significantly (P < 0.001) increased from 9.6 +/- 1.5% (control) to 26.9 +/- 3.3% and was inhibited by a monoclonal antibody against the VCAM-1 ligand, very late antigen-4. Analysis of VCAM-1 mRNA revealed synergism between IL-4 and LPS which may, in part, contribute to enhanced VCAM-1 expression. These results suggest that the presence of a co-stimulus such as LPS may be necessary for IL-4 to effectively induce VCAM-1 expression in lung microvasculature.