High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized Phospholipids
Neutrophil extracellular traps (NETs) are found in patients with various diseases, including cardiovascular diseases. We previously reported that copper-oxidized low-density lipoprotein (oxLDL) promotes NET formation of neutrophils, and that the resulting NETs increase the inflammatory responses of...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/13992 |
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| author | Hitomi Ohinata Takashi Obama Tomohiko Makiyama Yuichi Watanabe Hiroyuki Itabe |
| author_facet | Hitomi Ohinata Takashi Obama Tomohiko Makiyama Yuichi Watanabe Hiroyuki Itabe |
| author_sort | Hitomi Ohinata |
| collection | DOAJ |
| description | Neutrophil extracellular traps (NETs) are found in patients with various diseases, including cardiovascular diseases. We previously reported that copper-oxidized low-density lipoprotein (oxLDL) promotes NET formation of neutrophils, and that the resulting NETs increase the inflammatory responses of endothelial cells. In this study, we investigated the effects of high-density lipoproteins (HDL) on NET formation. HL-60-derived neutrophils were treated with phorbol 12-myristate 13-acetate (PMA) and further incubated with oxLDL and various concentrations of HDL for 2 h. NET formation was evaluated by quantifying extracellular DNA and myeloperoxidase. We found that the addition of native HDL partially decreased NET formation of neutrophils induced by oxLDL. This effect of HDL was lost when HDL was oxidized. We showed that oxidized phosphatidylcholines and lysophosphatidylcholine, which are generated in oxLDL, promoted NET formation of PMA-primed neutrophils, and NET formation by these products was completely blocked by native HDL. Furthermore, we found that an electronegative subfraction of LDL, LDL(–), which is separated from human plasma and is thought to be an in vivo oxLDL, was capable of promoting NET formation. These results suggest that plasma lipoproteins and their oxidative modifications play multiple roles in promoting NET formation, and that HDL acts as a suppressor of this response. |
| first_indexed | 2024-03-09T18:17:17Z |
| format | Article |
| id | doaj.art-060f2077804947d2886e4d9801000d85 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:17:17Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-060f2077804947d2886e4d9801000d852023-11-24T08:36:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221399210.3390/ijms232213992High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized PhospholipidsHitomi Ohinata0Takashi Obama1Tomohiko Makiyama2Yuichi Watanabe3Hiroyuki Itabe4Division of Biological Chemistry, Department of Pharmaceutical Sciences, Showa University School of Pharmacy, Tokyo 142-8555, JapanDivision of Biological Chemistry, Department of Pharmaceutical Sciences, Showa University School of Pharmacy, Tokyo 142-8555, JapanDivision of Biological Chemistry, Department of Pharmaceutical Sciences, Showa University School of Pharmacy, Tokyo 142-8555, JapanDivision of Biological Chemistry, Department of Pharmaceutical Sciences, Showa University School of Pharmacy, Tokyo 142-8555, JapanDivision of Biological Chemistry, Department of Pharmaceutical Sciences, Showa University School of Pharmacy, Tokyo 142-8555, JapanNeutrophil extracellular traps (NETs) are found in patients with various diseases, including cardiovascular diseases. We previously reported that copper-oxidized low-density lipoprotein (oxLDL) promotes NET formation of neutrophils, and that the resulting NETs increase the inflammatory responses of endothelial cells. In this study, we investigated the effects of high-density lipoproteins (HDL) on NET formation. HL-60-derived neutrophils were treated with phorbol 12-myristate 13-acetate (PMA) and further incubated with oxLDL and various concentrations of HDL for 2 h. NET formation was evaluated by quantifying extracellular DNA and myeloperoxidase. We found that the addition of native HDL partially decreased NET formation of neutrophils induced by oxLDL. This effect of HDL was lost when HDL was oxidized. We showed that oxidized phosphatidylcholines and lysophosphatidylcholine, which are generated in oxLDL, promoted NET formation of PMA-primed neutrophils, and NET formation by these products was completely blocked by native HDL. Furthermore, we found that an electronegative subfraction of LDL, LDL(–), which is separated from human plasma and is thought to be an in vivo oxLDL, was capable of promoting NET formation. These results suggest that plasma lipoproteins and their oxidative modifications play multiple roles in promoting NET formation, and that HDL acts as a suppressor of this response.https://www.mdpi.com/1422-0067/23/22/13992neutrophil extracellular trapshigh-density lipoprotein (HDL)oxidized low-density lipoprotein (oxLDL)oxidized phosphatidylcholineelectronegative low-density lipoprotein |
| spellingShingle | Hitomi Ohinata Takashi Obama Tomohiko Makiyama Yuichi Watanabe Hiroyuki Itabe High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized Phospholipids International Journal of Molecular Sciences neutrophil extracellular traps high-density lipoprotein (HDL) oxidized low-density lipoprotein (oxLDL) oxidized phosphatidylcholine electronegative low-density lipoprotein |
| title | High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized Phospholipids |
| title_full | High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized Phospholipids |
| title_fullStr | High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized Phospholipids |
| title_full_unstemmed | High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized Phospholipids |
| title_short | High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized Phospholipids |
| title_sort | high density lipoprotein suppresses neutrophil extracellular traps enhanced by oxidized low density lipoprotein or oxidized phospholipids |
| topic | neutrophil extracellular traps high-density lipoprotein (HDL) oxidized low-density lipoprotein (oxLDL) oxidized phosphatidylcholine electronegative low-density lipoprotein |
| url | https://www.mdpi.com/1422-0067/23/22/13992 |
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