Antibacterial responses by peritoneal macrophages are enhanced following vitamin D supplementation.
Antibacterial responses by peritoneal macrophages are enhanced following vitamin D supplementation.
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DOI：
10.1371/journal.pone.0116530
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hewison M
中科院分区：
文献类型：
--
作者：
Bacchetta J;Chun RF;Gales B;Zaritsky JJ;Leroy S;Wesseling-Perry K;Boregaard N;Rastogi A;Salusky IB;Hewison M
慢性肾脏病（CKD）患者通常表现出低血清25-羟基维生素D（25 D）和1，25-二羟基维生素D（1，25 D），感染风险高，特别是那些接受腹膜透析（PD）的患者。我们假设PD患者的腹腔巨噬细胞是维生素D诱导的抗菌活性的重要靶点。从27名未感染的PD患者中获得透析液流出液。流式细胞术显示PD细胞主要为单核细胞（37.9± 17.7%CD 14 +/CD 45+）。离体分析显示，用25 D（100 nM，6小时）或1，25 D（5 nM，6小时）处理的PD细胞诱导抗菌组织蛋白酶抑制素（CAMP）的mRNA，但相反地抑制铁调素（HAMP）的mRNA。来自腹膜炎患者（n = 3）的PD细胞相对于来自未感染患者的细胞显示出更高的CAMP（18倍±9，p<0.05）和HAMP（64倍±7）的基线表达。 在12名未感染的PD患者中，口服补充单剂量维生素D2（100，000 IU）使血清25 D水平从18±8 ng/ml增加至41±15 ng/ml（p = 0.002）。 这对PD细胞CD 14/CD 45表达没有显著影响，但HAMP的mRNA被显著抑制（0.5倍，p = 0.04）。 使用混合线性统计模型对PD细胞CD 14/CD 45表达进行调整也显示补充维生素D的患者中CAMP（PD细胞中的mRNA和流出液中的蛋白质）表达增加。这些数据首次表明，体外和体内补充维生素D可促进先天免疫反应，从而可能增强PD患者的巨噬细胞抗菌反应。这突出了维生素D在预防CKD感染相关并发症方面的潜在重要功能。
Patients with chronic kidney disease (CKD), who usually display low serum 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are at high risk of infection, notably those undergoing peritoneal dialysis (PD). We hypothesized that peritoneal macrophages from PD patients are an important target for vitamin D-induced antibacterial activity. Dialysate effluent fluid was obtained from 27 non-infected PD patients. Flow cytometry indicated that PD cells were mainly monocytic (37.9±17.7% cells CD14+/CD45+). Ex vivo analyses showed that PD cells treated with 25D (100 nM, 6 hrs) or 1,25D (5 nM, 6 hrs) induced mRNA for antibacterial cathelicidin (CAMP) but conversely suppressed mRNA for hepcidin (HAMP). PD cells from patients with peritonitis (n = 3) showed higher baseline expression of CAMP (18-fold±9, p<0.05) and HAMP (64-fold±7) relative to cells from non-infected patients. In 12 non-infected PD patients, oral supplementation with a single dose of vitamin D2 (100,000 IU) increased serum levels of 25D from 18±8 to 41±15 ng/ml (p = 0.002). This had no significant effect on PD cell CD14/CD45 expression, but mRNA for HAMP was suppressed significantly (0.5-fold, p = 0.04). Adjustment for PD cell CD14/CD45 expression using a mixed linear statistical model also revealed increased expression of CAMP (mRNA in PD cells and protein in effluent) in vitamin D-supplemented patients. These data show for the first time that vitamin D supplementation in vitro and in vivo promotes innate immune responses that may enhance macrophage antibacterial responses in patients undergoing PD. This highlights a potentially important function for vitamin D in preventing infection-related complications in CKD.
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DOI：
10.1053/j.ajkd.2008.11.017
发表时间：
2009-03-01
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.8
作者：
Bacchetta, Justine;Dubourg, Laurence;Cochat, Pierre
通讯作者：
Cochat, Pierre
影响因子：
19.6
作者：
GOLDSTEIN, CS;BOMALASKI, JS;DOUGLAS, SD
通讯作者：
DOUGLAS, SD
影响因子：
3
作者：
Bouts, AHM;Davin, JC;Out, TA
通讯作者：
Out, TA
影响因子：
4.1
作者：
Hewison M
通讯作者：
Hewison M