Basiouni Shereen, Fuhrmann Herbert, Schumann Julia
Institute of Physiological Chemistry, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, An den Tierkliniken 1, 04103 Leipzig, Germany.
Int J Mol Sci. 2013 Apr 25;14(5):9005-17. doi: 10.3390/ijms14059005.
The impact of polyunsaturated fatty acid (PUFA) supplementation on phospholipase D (PLD) trafficking and activity in mast cells was investigated. The enrichment of mast cells with different PUFA including α-linolenic acid (LNA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA) or arachidonic acid (AA) revealed a PUFA-mediated modulation of the mastoparan-stimulated PLD trafficking and activity. All PUFA examined, except AA, prevented the migration of the PLD1 to the plasma membrane. For PLD2 no PUFA effects on trafficking could be observed. Moreover, PUFA supplementation resulted in an increase of mastoparan-stimulated total PLD activity, which correlated with the number of double bonds of the supplemented fatty acids. To investigate, which PLD isoform was affected by PUFA, stimulated mast cells were supplemented with DHA or AA in the presence of specific PLD-isoform inhibitors. It was found that both DHA and AA diminished the inhibition of PLD activity in the presence of a PLD1 inhibitor. By contrast, only AA diminished the inhibition of PLD activity in the presence of a PLD2 inhibitor. Thus, PUFA modulate the trafficking and activity of PLD isoforms in mast cells differently. This may, in part, account for the immunomodulatory effect of unsaturated fatty acids and contributes to our understanding of the modulation of mast cell activity by PUFA.
研究了多不饱和脂肪酸(PUFA)补充剂对肥大细胞中磷脂酶D(PLD)转运和活性的影响。用不同的PUFA(包括α-亚麻酸(LNA)、二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)、亚油酸(LA)或花生四烯酸(AA))富集肥大细胞,结果显示PUFA对mastoparan刺激的PLD转运和活性具有介导调节作用。除AA外,所有检测的PUFA均阻止了PLD1向质膜的迁移。对于PLD2,未观察到PUFA对其转运有影响。此外,补充PUFA导致mastoparan刺激的总PLD活性增加,这与补充脂肪酸的双键数量相关。为了研究哪种PLD同工型受PUFA影响,在存在特异性PLD同工型抑制剂的情况下,用DHA或AA补充受刺激的肥大细胞。结果发现,在存在PLD1抑制剂的情况下,DHA和AA均减弱了对PLD活性的抑制作用。相比之下,在存在PLD2抑制剂的情况下,只有AA减弱了对PLD活性的抑制作用。因此,PUFA对肥大细胞中PLD同工型的转运和活性的调节方式不同。这可能部分解释了不饱和脂肪酸的免疫调节作用,并有助于我们理解PUFA对肥大细胞活性的调节。