Phosphatidic Acid and Lysophosphatidic Acid Induce Haptotactic Migration of Human Monocytes (*)
Phosphatidic Acid and Lysophosphatidic Acid Induce Haptotactic Migration of Human Monocytes (*)
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磷脂酸和溶血磷脂酸诱导人单核细胞趋触迁移 (*)
DOI：
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发表时间：
1995
影响因子：
4.8
通讯作者：
S. Sozzani
中科院分区：
文献类型：
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作者：
D. Zhou;W. Luini;S. Bernasconi;L. Diomede;M. Salmona;A. Mantovani;S. Sozzani
本研究旨在确定磷脂酸的趋化活性，磷脂酸是吞噬细胞在对趋化激动剂作出反应时迅速产生的。外源性添加的磷脂酸诱导人单核细胞穿过聚碳酸酯滤膜定向迁移，其效力（迁移的细胞数量）与“经典”趋化因子相当。在脂质特异性研究中，磷脂酸的活性随着酰基链长度的增加而降低，但通过在酰基链中引入不饱和键可恢复活性，其中活性最强的形式是天然存在的18:0,20:4 - 磷脂酸。溶血磷脂酸在诱导单核细胞迁移方面也有活性。测试的其他磷脂和溶血磷脂在这种反应中均无效。在没有可检测到的可溶性趋化因子的情况下，单核细胞的迁移受结合在聚碳酸酯滤膜上的磷脂酸和溶血磷脂酸的梯度调节。如果磷脂结合在纤连蛋白包被的聚碳酸酯滤膜上，也能观察到迁移现象。因此，磷脂酸和溶血磷脂酸与其他生理趋化剂（例如C5a和白细胞介素 - 8）类似，通过一种趋触性机制诱导细胞迁移。磷脂酸导致丝状肌动蛋白迅速增加，并且在较高浓度下，诱导细胞内钙浓度升高。百日咳博德特氏菌毒素以浓度依赖的方式抑制单核细胞向磷脂酸和溶血磷脂酸的迁移，但不抑制向二酰基甘油的迁移，而霍乱毒素则无效。在趋化试验中，磷脂酸和溶血磷脂酸诱导完全的同源脱敏，并且彼此之间或与二酰基甘油和单核细胞趋化蛋白 - 1仅部分交叉脱敏。苏拉明抑制单核细胞趋化的效率不同：磷脂酸>溶血磷脂酸>二酰基甘油。相反，单核细胞趋化蛋白 - 1诱导的趋化作用不受该药物影响。总体而言，这些数据表明磷脂酸诱导单核细胞的趋触性迁移，这种迁移至少部分是受体介导的。这些结果支持磷脂酸和溶血磷脂酸在调节白细胞在组织中积聚方面的作用。
The present study was aimed at defining the chemotactic activity of phosphatidic acid, which is rapidly produced by phagocytes in response to chemotactic agonists. Exogenously added phosphatidic acid induced human monocyte directional migration across polycarbonate filters with an efficacy (number of cell migrated) comparable to that of “classical” chemotactic factors. In lipid specificity studies, activity of phosphatidic acid decreased with increasing acyl chain length but was restored by introducing unsaturation in the acyl chain with the most active form being the natural occurring 18:0,20:4-phosphatidic acid. Lysophosphatidic acid was also active in inducing monocyte migration. No other phospholipid and lysophospholipid tested was effective in this response. Monocyte migration was regulated by a gradient of phosphatidic acid and lysophosphatidic acid bound to the polycarbonate filter, in the absence of detectable soluble chemoattractant. Migration was also observed if phospholipids were bound to fibronectin-coated polycarbonate filters. Thus, phosphatidic acid and lysophosphatidic acid, similarly to other physiological chemoattractants (e.g. C5a and interleukin-8), induce cell migration by an haptotactic mechanism. Phosphatidic acid caused a rapid increase of filamentous actin and, at higher concentrations, induced a rise of intracellular calcium concentration. Monocyte migration to phosphatidic acid and lysophosphatidic acid, but not to diacylglycerol, was inhibited in a concentration-dependent manner by Bordetella pertussis toxin, while cholera toxin was ineffective. In the chemotactic assay, phosphatidic acid and lysophosphatidic acid induced a complete homologous desensitization and only partially cross-desensitized one with each other, or with diacylglycerol and monocyte chemotactic protein-1. Suramine inhibited monocyte chemotaxis with a different efficiency: phosphatidic acid > lysophosphatidic acid diacylglycerol. On the contrary, monocyte chemotactic protein-1-induced chemotaxis was not affected by the drug. Collectively, these data show that phosphatidic acid induces haptotactic migration of monocytes that is at least in part receptor-mediated. These results support a role for phosphatidic acid and lysophosphatidic acid in the regulation of leukocyte accumulation into tissues.