Eghtesad M, Jackson H E, Cunningham A C
School of Sciences, University of Sunderland, Sunderland, UK.
Immunology. 2001 Feb;102(2):157-64. doi: 10.1046/j.1365-2567.2001.01172.x.
The ability of freshly isolated primary human alveolar epithelial cells (type II pneumocytes) to induce leucocyte migration across an endothelial monolayer was investigated. Three-way factorial analysis of variance (ANOVA) demonstrated that resting alveolar endothelial cells (AEC) could produce detectable quantities of monocyte chemoattractant protein 1 (MCP-1), which was upregulated in response to tumour necrosis factor-alpha (TNF-alpha) in a dose- and time-dependent fashion. Interferon-gamma (IFN-gamma) had no significant effect on this process. TNF-alpha and IFN-gamma both induced AEC to provoke migration of CD14+ monocytes and CD3+ lymphocytes across endothelium. IFN-gamma and TNF-alpha synergized in their ability to induce production of T lymphocyte, but not monocyte, chemoattractants from AEC. Leucocyte transendothelial migration was inhibited by anti-MCP-1 neutralizing antibody and by heparin, a polyanionic glycosaminoglycan (GAG). These data suggest that human AEC play a role in the multiple mechanisms that facilitate monocyte and T lymphocyte migration into the alveolar compartment of the lung under homeostasis and inflammatory conditions. One of these mechanisms is mediated via constitutive MCP-1 production by alveolar epithelial cells, which is upregulated by TNF-alpha.
研究了新鲜分离的原代人肺泡上皮细胞（II型肺细胞）诱导白细胞穿过内皮细胞单层迁移的能力。三因素方差分析（ANOVA）表明，静息肺泡内皮细胞（AEC）可产生可检测量的单核细胞趋化蛋白1（MCP-1），其在肿瘤坏死因子-α（TNF-α）作用下呈剂量和时间依赖性上调。γ干扰素（IFN-γ）对该过程无显著影响。TNF-α和IFN-γ均诱导AEC促使CD14+单核细胞和CD3+淋巴细胞穿过内皮迁移。IFN-γ和TNF-α协同诱导AEC产生T淋巴细胞而非单核细胞趋化因子。白细胞跨内皮迁移受到抗MCP-1中和抗体和肝素（一种聚阴离子糖胺聚糖（GAG））的抑制。这些数据表明，人AEC在促进单核细胞和T淋巴细胞在稳态和炎症条件下迁移至肺肺泡腔的多种机制中发挥作用。其中一种机制是由肺泡上皮细胞组成性产生MCP-1介导的，其受TNF-α上调。
