Polymorphonuclear leukocytes modulate tissue factor production by mononuclear cells:: Role of reactive oxygen species
Polymorphonuclear leukocytes modulate tissue factor production by mononuclear cells:: Role of reactive oxygen species
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DOI：
10.4049/jimmunol.164.7.3822
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发表时间：
2000-04-01
影响因子：
4.4
通讯作者：
Plaisancié, H
中科院分区：
文献类型：
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作者：
Cadroy, Y;Dupouy, D;Plaisancié, H
为了确定多形核白细胞 (PMN) 是否调节单核细胞产生组织因子 (TF)，将 PBMC 与浓度逐渐增加的 PMN 一起孵育，PMN 不表达任何促凝血活性。共培养20小时后，PMN增强或抑制PBMC的TF产生，这种作用取决于PMN/PBMC的比例。当比率从 1/1000 增加到 1/5 时，无论是否有 LPS，PBMC 的 TF 活性均增加至基线值的 2.5 倍峰值（p < 0.01），TF Ag 和 TF mRNA 也增加。这种增强作用是由共培养期间 PMN 释放的活性氧 (ROS) 介导的； PMN与PBMC之间不需要直接的细胞接触，当PMN受到fMLP（一种趋化肽）刺激时，其增强，并且被两种抗氧化剂N-乙酰半胱氨酸和吡咯烷二硫代氨基甲酸盐所抑制，相反，当PR PMN/PBMC比率进一步从1/2增加到2/1时，与培养的PBMC相比，PBMC TF活性、Ag和mRNA降低并受到抑制单独（p < 0.01）。这种抑制作用需要 PMN 和 PBMC 之间的直接细胞接触，而不是由于 PMN 介导的细胞毒性。为了证实ROS的作用，H2O2以剂量依赖性方式增强然后抑制PBMC的TF活性，类似于PMN，因此，PMN可能通过释放ROS对PBMC的TF产生发挥浓度依赖性调节作用，从而在血栓形成和动脉粥样硬化的发病机制中发挥重要作用。
To determine whether polymorphonuclear leukocytes (PMN) modulate the production of tissue factor (TF) by monocytes, PBMC were incubated with increasing concentrations of PMN, PMN did not express any procoagulant activity. After 20-h cocultures, PMN enhanced or inhibited the TF production of PBMC, and this effect depended on the PMN/PBMC ratio. When the ratio increased from 1/1000 to 1/5, without or with LPS, the TF activity of PBMC increased to peak at 2.5-fold the baseline value (p < 0.01), The TF Ag and TF mRNA also increased. This potentiating effect was mediated by reactive oxygen species (ROS) released by PMN during the coculture; it did not require direct cell contact between PMN and PBMC, it was enhanced when PMN were stimulated by fMLP (a chemotactic peptide), and it was inhibited by two antioxidants, N-acetyl cysteine and pyrrolidine dithiocarbamate, In contrast, when the PR PMN/PBMC ratio was further increased from 1/2 to 2/1, the PBMC TF activity, Ag, and mRNA decreased and were inhibited compared with those of PBMC cultured alone (p < 0.01). This inhibitory effect required direct cell contact between PMN and PBMC, and it was not due to a PMN-mediated cytotoxicity. To confirm the role of ROS, H2O2 enhanced then inhibited the TF activity of PBMC in a dose-dependent manner, similarly to PMN, Thus, PMN may play an important role in the pathogenesis of thrombosis and atherosclerosis by exerting concentration-dependent regulatory effects on the TF production by PBMC via the release of ROS.