Effects of methylprednisolone administration on lymphocyte LECAM-1, CD44, and LFA-1 expression. Implications for steroid-induced lymphopenia.
Effects of methylprednisolone administration on lymphocyte LECAM-1, CD44, and LFA-1 expression. Implications for steroid-induced lymphopenia.
复制标题
甲基泼尼松龙给药对淋巴细胞 LECAM-1、CD44 和 LFA-1 表达的影响。
DOI：
10.1111/j.1749-6632.1993.tb17183.x
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发表时间：
1993
影响因子：
5.2
通讯作者：
Sackstein,R
中科院分区：
文献类型：
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作者：
Sackstein,R
皮质类固醇治疗导致免疫抑制，部分原因是消耗了成熟的淋巴细胞循环池的血液。这种短暂性淋巴细胞减少是由于淋巴细胞向外周淋巴结的运输受到抑制，导致循环细胞重新分布到其他组织区室，如骨。淋巴细胞向淋巴结迁移（“归巢”）的第一步涉及细胞特异性附着在淋巴结高内皮小静脉（HEV）上。LECAM-1 （l -选择素）是一种90000 mw的淋巴细胞糖蛋白，介导HEV的附着，是“淋巴结归巢受体”。除了该蛋白外，还鉴定了两个辅助hev结合分子：LFA-1 （CDlla/CD18）和CD44。尽管对这些蛋白的生物化学和皮质类固醇治疗后淋巴细胞迁移的大量生理学研究有广泛的了解，但我们对类固醇诱导淋巴细胞迁移到淋巴结减少的潜在分子机制的了解尚不完整。在啮齿类动物中，有证据表明类固醇可能降低HEV结合淋巴细胞的能力。在人类中，这种作用尚未得到证实，可能假设类固醇降低了促进进入淋巴结的淋巴细胞粘附分子的表达。本研究旨在通过分析甲基强的松龙对淋巴细胞LECAh4-1、CD44和LFA-1表达的体内和体外影响来解决这一问题。在组织培养研究和体内脉冲注射甲基强的松龙后，用密度离心分离的外周血淋巴细胞进行了流式细胞术分析。6名健康志愿者在15分钟内注射生理盐水（安慰剂）和甲基强的松龙（Solumedrol， 3 mg/kg生理盐水），并在注射前、注射后以及注射后1、2、4、8、24和48小时分离外周血淋巴细胞。生理盐水输注（安慰剂）对淋巴细胞计数或淋巴细胞LECAM-1、CD44或LFA-1 （cdla和CD18链）的表达水平没有影响。类固醇输注后，淋巴细胞减少
Corticosteroid therapy causes immunosuppression in part by depleting the bloodstream of the mature, recirculating pool of lymphocytes. This transient lymphopenia results from an inhibition of lymphocyte trafficking to peripheral lymph nodes, leading to a redistribution of circulating cells to other tissue compartments, such as bone The first step in the migration (“homing”) of lymphocytes to lymph node involves the specific attachment of the cells to lymph node high endothelial venules (HEV). 4 LECAM-1 (L-selectin), a 90,000 mw lymphocyte glycoprotein which mediates attachment to HEV, is the “lymph node homing receptor.” In addition to this protein, two accessory HEV-binding molecules have also been identified: LFA-1 (CDlla/CD18) and CD44. Despite extensive knowledge of the biochemistry of these proteins and numerous physiologic studies of lymphocyte migration following corticosteroid therapy, our knowledge into the underlying molecular mechanisms for the steroid-induced decrease in lymphocyte migration to lymph nodes is incomplete. In rodents, there is evidence that steroids may decrease the capacity of HEV to bind lymphocytes. 5, h In humans, this effect has not been demonstrated, and it may be hypothesized that steroids decrease expression of lymphocyte adhesion molecules specific for promoting entry into lymph node. The present study was undertaken to address this issue by analyzing the in vivo and in vitro effects of methylprednisolone on lymphocyte LECAh4-1, CD44, and LFA-1 expression.Flow cytometric analysis of peripheral blood lymphocytes isolated by density centrifugation was performed in tissue culture studies and following pulse methylprednisolone infusion in vivo. Six healthy volunteers underwent infusions of saline (placebo) and methylprednisolone (Solumedrol, 3 mg/kg in saline) over 15 minutes, and peripheral blood lymphocytes were isolated before, immediately after, and at 1, 2, 4, 8, 24, and 48 hours following infusions. Saline infusion (placebo) had no effect on lymphocyte counts or on the levels of expression of lymphocyte LECAM-1, CD44, or LFA-1 (both CDlla and CD18 chains). Following steroid infusion, lymphopenia