Leukotriene D4 Upregulates Oxidized Low-Density Lipoprotein Receptor 1 and CD36 to Enhance Oxidized LDL Uptake and Phagocytosis in Macrophages Through Cysteinyl Leukotriene Receptor 1
| Autor: | Sailaja Paruchuri, Ernest Duah, Charles K. Thodeti, Lakshminarayan Reddy Teegala, Sabita Pokhrel, Ravindra Gudneppanavar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Leukotriene D4
Physiology CD36 Phagocytosis Inflammation chemistry.chemical_compound Physiology (medical) medicine OLR1 QP1-981 Macrophage Foam cell Original Research oxLDL biology phagocytosis respiratory system Cell biology Cysteinyl leukotriene receptor 1 chemistry LTD4 biology.protein lipids (amino acids peptides and proteins) medicine.symptom CysLT1R atherosclerosis MCP-1 |
| Zdroj: | Frontiers in Physiology Frontiers in Physiology, Vol 12 (2021) |
| ISSN: | 1664-042X |
| Popis: | Endothelial permeability, leukocyte attachment, and unregulated oxidized LDL (oxLDL) uptake by macrophages leading to the formation of foam cells are all vital in the initiation and progression of atherosclerosis. During inflammation, several inflammatory mediators regulate this process through the expression of distinct oxLDL binding cell surface receptors on macrophages. We have previously shown that Leukotriene D4 (LTD4) promotes endothelial dysfunction, increasing endothelial permeability and enhancing TNFα-mediated attachment of monocytes to endothelium, which hints at its possible role in atherosclerosis. Here we analyzed the effect of LTD4 on macrophage function. Macrophages mainly express CysLT1R and flux calcium in response to LTD4. Further, LTD4 potentiates phagocytosis in macrophages as revealed by the uptake of zymosan particles. Notably, LTD4 augmented macrophage phagocytosis and oxLDL uptake which is sensitive to MK-571 [Montelukast (MK)], a CysLT1R-specific antagonist. Mechanistically, LTD4 upregulated two receptors central to foam cell formation, oxidized low-density lipoprotein receptor-1 (OLR1/LOX-1), and CD36 in a time and dose-dependent manner. Finally, LTD4 enhanced the secretion of chemokines MCP-1 and MIP1β. Our results suggest that LTD4 contributes to atherosclerosis either through driving foam cell formation or recruitment of immune cells or both. CysLT1R antagonists are safely being used in the treatment of asthma, and the findings from the current study suggest that these can be re-purposed for the treatment of atherosclerosis. |
| Databáze: | OpenAIRE |
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