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1α,25 - 二羟维生素D3增强单核细胞趋化性。对艾滋病患者迁移缺陷的刺激作用。

Augmentation of monocyte chemotaxis by 1 alpha,25-dihydroxyvitamin D3. Stimulation of defective migration of AIDS patients.

作者信息

Girasole G, Wang J M, Pedrazzoni M, Pioli G, Balotta C, Passeri M, Lazzarin A, Ridolfo A, Mantovani A

机构信息

Istituto di Clinica Medica Generale e Terapia, Università di Parma, Italy.

出版信息

J Immunol. 1990 Oct 15;145(8):2459-64.

PMID:2212648
Abstract

Preincubation for 20 h with 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) markedly augmented the chemotactic responsiveness of human blood monocytes to the classical chemoattractant, FMLP. A modest enhancement of monocyte spontaneous locomotion in the absence of chemoattractants was also observed. Maximal increase of monocyte migration was observed after pretreatment with 10(-9) M 1,25(OH)2D3 and was detectable at FMLP concentrations ranging from 10(-10) to 10(-7) M. Pretreatment with 1,25(OH)2D3 augmented the number of monocyte high affinity FMLP receptors (1500 +/- 220 and 3800 +/- 300 sites per cell for untreated and 1,25(OH)2D3-pretreated cells, respectively) with no significant changes in Kd values (2 +/- 0.5 nM and 4 +/- 1 nM, for untreated and 1,25(OH)2D3-pretreated monocytes). Enhanced chemotaxis was not restricted to FMLP, because 1,25(OH)2D3-treated monocytes showed enhanced migration also in response to activated C components and chemotactic cytokines. In agreement with previous observations, monocytes from AIDS patients showed defective migration capacity. In vitro exposure to 1,25(OH)2D3 stimulated monocyte migration in all 10 patients examined with considerable quantitative differences among individuals. Regulating the responsiveness of mature monocytes to chemo-attractants, 1,25(OH)2D3, produced systemically or in situ by immunocompetent cells, could play a role in the regulation of the recruitment of monocytes at sites of inflammation, cell-mediated immunity, or bone resorption. The potential of 1,25(OH)2D3 as a restorative agent under conditions of defective phagocyte recruitment deserves further exploration.

摘要

用1α,25 - 二羟基维生素D3(1,25(OH)2D3)预孵育20小时,可显著增强人血单核细胞对经典趋化因子FMLP的趋化反应性。在没有趋化因子的情况下,还观察到单核细胞自发运动有适度增强。用10(-9) M 1,25(OH)2D3预处理后,单核细胞迁移出现最大增加,在FMLP浓度范围为10(-10)至10(-7) M时可检测到。用1,25(OH)2D3预处理可增加单核细胞高亲和力FMLP受体的数量(未处理细胞和1,25(OH)2D3预处理细胞分别为每细胞1500±220和3800±300个位点),而Kd值无显著变化(未处理和1,25(OH)2D3预处理单核细胞分别为2±0.5 nM和4±1 nM)。增强的趋化作用并不局限于FMLP,因为1,25(OH)2D3处理的单核细胞对活化的补体成分和趋化细胞因子也表现出增强的迁移。与先前的观察结果一致,艾滋病患者的单核细胞显示出有缺陷的迁移能力。在体外,对所有10名接受检查的患者,1,25(OH)2D3刺激单核细胞迁移,个体之间存在相当大的数量差异。由免疫活性细胞在全身或原位产生的1,25(OH)2D3调节成熟单核细胞对趋化因子的反应性,可能在炎症部位、细胞介导的免疫或骨吸收部位单核细胞募集的调节中发挥作用。1,25(OH)2D3在吞噬细胞募集缺陷情况下作为恢复剂的潜力值得进一步探索。

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