Monocyte phenotyping and management of lipoprotein X syndrome.
Monocyte phenotyping and management of lipoprotein X syndrome.
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DOI：
10.1016/j.jacl.2020.08.012
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发表时间：
2020-11
影响因子：
4.4
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Lian Z;Saeed A;Peng X;Perrard XD;Jia X;Hussain A;Ballantyne CM;Wu H
脂蛋白X（LpX）在血液中的积累可导致严重的高胆固醇血症和皮肤黄瘤。单核细胞敏感地感知循环中的脂质变化并促进炎症。然而，单核细胞如何响应LpX是不确定的。我们研究了单核细胞的表型，从受试者，谁LpX，严重的高胆固醇血症，广泛的皮肤黄色瘤，和半选择性血浆置换疗法（SPPT）的影响。使用趋化激活细胞分选和粘附试验来检查单核细胞表型和离体oxLDL摄取和粘附在患者治疗前后与SPPT。测定来自患者的血浆对来自健康受试者的单核细胞的表型和粘附的影响。SPPT可改善高胆固醇血症和皮肤黄瘤。治疗前，患者的非经典单核细胞频率低于对照受试者，但中间单核细胞频率高于对照受试者。治疗前，与对照组相比，LpX患者的单核细胞显示出更多的细胞内脂质积聚、几种细胞表面标志物和细胞内细胞因子的改变以及oxLDL摄取增强和粘附减少。SPPT后，来自LpX患者的单核细胞的表型与对照单核细胞相似。与来自对照受试者或治疗后患者的血浆相比，与来自治疗前患者的血浆孵育增加了来自健康受试者的单核细胞的CD11c表达和粘附。脂蛋白X诱导的高胆固醇血症增加了脂质积聚，改变了单核细胞的表型，这可能有助于皮肤黄色瘤的发展。通过SPPT去除LpX减少了脂质积聚并改善了单核细胞表型，可能有助于黄色瘤消退。
Accumulation of lipoprotein X (LpX) in blood can cause severe hypercholesterolemia and cutaneous xanthomas. Monocytes sensitively sense lipid changes in circulation and contribute to inflammation. However, how monocytes respond to LpX is undefined. We examined the phenotype of monocytes from a subject, who had LpX, severe hypercholesterolemia, and extensive cutaneous xanthomas, and effects of semiselective plasmapheresis therapy (SPPT). Fluorescence-activated cell sorting and adhesion assays were used to examine monocyte phenotype and ex vivo oxLDL uptake and adhesion in the patient before and after treatment with SPPT. Effects of plasma from the patient on the phenotype and adhesion of monocytes from a healthy subject were determined. SPPT improved hypercholesterolemia and cutaneous xanthomas. Before treatment, the patient had lower frequency of non-classical monocytes but higher frequency of intermediate monocytes than control subject. Before treatment, monocytes from the LpX patient showed more intracellular lipid accumulation, alterations in several cell surface markers and intracellular cytokines as well as enhanced oxLDL uptake and reduced adhesion compared to control. After SPPT, the phenotypes of monocytes from the LpX patient were similar to control monocytes. Incubation with plasma from the patient before treatment as compared to plasma from the control subject or the patient after treatment increased CD11c expression and adhesion of monocytes from a healthy subject. LpX-induced hypercholesterolemia increased lipid accumulation and altered the phenotype of monocytes, which may contribute to cutaneous xanthoma development. Removal of LpX by SPPT reduced lipid accumulation and improved monocyte phenotype, likely contributing to xanthoma resolution.
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影响因子：
5.8
作者：
Khan, Ilvira M.;Pokharel, Yashashwi;Ballantyne, Christie M.
通讯作者：
Ballantyne, Christie M.
DOI：
10.1073/pnas.75.7.3459
发表时间：
1978-01-01
影响因子：
11.1
作者：
FELKER, TE;HAMILTON, RL;HAVEL, RJ
通讯作者：
HAVEL, RJ
影响因子：
15.9
作者：
SEIDEL, D;ALAUPOVIC, P;MCCONATHY, WJ
通讯作者：
MCCONATHY, WJ
影响因子：
8.8
作者：
Saja MF;Baudino L;Jackson WD;Cook HT;Malik TH;Fossati-Jimack L;Ruseva M;Pickering MC;Woollard KJ;Botto M
通讯作者：
Botto M
影响因子：
39.3
作者：
Moens, Sophie J. Bernelot;Neele, Annette E.;Stroes, Erik S. G.
通讯作者：
Stroes, Erik S. G.