Cocaine enhances monocyte migration across the blood-brain barrier. Cocaine's connection to AIDS dementia and vasculitis?
Cocaine enhances monocyte migration across the blood-brain barrier. Cocaine's connection to AIDS dementia and vasculitis?
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DOI：
10.1007/978-1-4615-5347-2_22
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发表时间：
1998
影响因子：
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通讯作者：
Milan Fiala;Xiaohu Gan;Ling Zhang;Steven D. House;Thomas F. Newton;M. C. Graves;Paul Shapshak
中科院分区：
文献类型：
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作者：
Milan Fiala;Xiaohu Gan;Ling Zhang;Steven D. House;Thomas F. Newton;M. C. Graves;Paul Shapshak
可卡因对免疫和神经内分泌系统具有广泛的影响（Fiala等人，1996），类似于具有促炎细胞因子上调和HPA轴刺激的炎性“应激”反应（Gan等，1997年）。可卡因滥用还与血管病变有关，包括血管炎、血管痉挛和出血。这些作用表明可卡因可扰乱内皮细胞（包括血脑屏障）的功能，并影响HIV感染个体向AIDS的进展（Shapshak等人，1997; Goodkin等人，1997年）。为了了解可卡因滥用的临床后果，重要的是要深入了解可卡因对免疫和内皮细胞作用的分子和细胞基础。可卡因对（a）渗透性，（B）免疫细胞迁移，（c）粘附分子，和（d）在血液中研究细胞因子表达。用脑微血管内皮细胞和胎儿星形胶质细胞构建脑屏障模型，结果如下：（a）可卡因和肿瘤坏死因子-α（TNF-α）以类似的剂量反应方式增加模型对菊粉的渗透性;（B）可卡因（10 ~（-4）~ 10 ~（-8）M）促进单核细胞跨膜迁移，10 ~（-5）M可卡因使单核细胞迁移率最大，约为100%;（c）可卡因处理还增加了内皮粘附分子、细胞间粘附分子-1（ICAM-1）血管细胞粘附分子-1（VCAM-1）和血小板/内皮细胞粘附分子-1（PECAM-1）;（d）尽管由于个体之间反应程度的异质性，可卡因对单核细胞产生细胞因子的体外作用难以评估，这些数据表明，可卡因成瘾者的单核细胞在体外对可卡因激发具有高分泌的炎性细胞因子的敏感性。（A）大鼠的慢性可卡因治疗显著增加了滚动的白色血细胞流量，白细胞-内皮细胞粘附，和ICAM-1在肠系膜中的表达（House等，1996）;（B）向可卡因依赖性受试者注射可卡因使单核细胞分泌的细胞因子平衡向Th 1型倾斜（Gan等，1997），和（C）可卡因注射刺激下丘脑-垂体轴（HPA）以增加抗炎和促炎激素分泌。总的来说，这些结果表明，可卡因对内皮细胞、免疫细胞和神经内分泌细胞的免疫作用损害了血脑屏障的功能，增加了细胞从血管的迁移，特别是迁移到大脑中，并可能引起血管炎。这些影响也可能增加HIV-1进入大脑的输入。
Cocaine has wide-ranging effects on the immune and neuroendocrine systems (Fiala et al., 1996) resembling an inflammatory “stress” response with upregulation of pro-inflammatory cytokines and stimulation of the HPA axis (Gan et al., 1997). Cocaine abuse has also been associated with vascular pathology, including vasculitis, vasospasm and hemorrhage. These effects suggest that cocaine could perturb the function of endothelial cells, including the blood—brain barrier, and influence the progression to AIDS in HIV-in- fected individuals (Shapshak et al, 1997; Goodkin et al., 1997). In order to understand clinical consequences of cocaine abuse, it is important to gain insight into molecular and cellular basis of cocaine’s effects on immune and endothelial cells.Cocaine’sin vitroeffects on (a) permeability, (b) immune cell migration, (c) adhesion molecules, and (d) cytokine expression were investigated in a blood—brain barrier model constructed with brain microvascular endothelial cells and fetal astrocytes with the following results: (a) cocaine and tumor necrosis factor-α (TNF-α) increased the model’s permeability to inulin similarly in a dose-responsive fashion; (b) cocaine (10-4to 10-8M) enhanced monocyte migration across the barrier with the maximum increase, approximately 100%, by 10-5M cocaine; (c) cocaine treatment also increased the expression of endothelial adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecules-1 (VCAM-1) and platelet/endothelial cell adhesion molecule-1 (PECAM-1); (d) although the cocainein vitroeffects on cytokine production by mononuclear cells have been difficult to assess due to a heterogeneity in the degree of responsiveess between individuals, the data suggest that mononuclear cells from cocaine addicts are sensitized toin vitrococaine challenge with hypersecretion of inflammatory cytokines.Cocaine’sin vivomanifestations are compatible with thesein vitroeffects: (A) chronic cocaine treatment of rats significantly increased rolling white blood cell flux, leukocyte-endothelium adhesion, and ICAM-1 expression in the mesentery (House et al., 1996); (B) cocaine injection to cocaine-dependent subjects tipped the balance of cytokine secretion by mononuclear cells to Thl-type (Gan et al., 1997), and (C) cocaine injection stimulated the hypothalamic-pituitary axis (HPA) to increase both anti- and pro-inflammatory hormonal secretion. Collectively, these results suggest that the immune effects of cocaine on endothelial, immune and neuroendocrine cells impair the function of the blood—brain barrier, increase cell emigration from the blood vessels, in particular into the brain, and may cause vasculitis. These effects could also increase importation of HIV-1 into the brain.