免疫抑制剂霉酚酸酯对单核细胞/内皮细胞相互作用及单核细胞黏附分子表达的抑制作用

Inhibition of monocyte/endothelial cell interactions and monocyte adhesion molecule expression by the immunosuppressant mycophenolate mofetil.

作者信息

Glomsda B A, Blaheta R A, Hailer N P

机构信息

University Hospital for Orthopaedic Surgery Friedrichsheim, Frankfurt am Main, Germany.

出版信息

Spinal Cord. 2003 Nov;41(11):610-9. doi: 10.1038/sj.sc.3101512.

DOI:10.1038/sj.sc.3101512

PMID:14569262

Abstract

STUDY DESIGN

In vitro study on the effects of mycophenolate mofetil (MMF) on isolated human monocytes and endothelial cells.

OBJECTIVES

Haematogenous macrophages play an essential role in the development of secondary damage following spinal cord injury (SCI), and there is evidence that the use of immunosuppressants such as MMF can reduce monocyte invasion and neuronal damage.

SETTING

University Hospital for Orthopaedic Surgery, Frankfurt am Main, Germany.

METHODS

The effects of MMF on the adhesion of human monocytes to human umbilical vein endothelial cells (HUVEC), monocyte binding to immobilised E-selectin, and monocyte expression of intercellular adhesion molecule (ICAM)-1, sialyl Lewis X (sLeX) and major histocompatibility complex (MHC)-II were studied. The binding of monocytes to E-selectin was examined by using purified and immobilised E-selectin fusion protein. Adhesion molecule expression was investigated by flow cytometry.

RESULTS

The binding of monocytes to HUVEC was significantly reduced by 30.1% after treatment of monocytes with MMF (10 microg/ml), whereas the pretreatment of HUVEC with MMF did not result in significant changes in monocyte adhesion. MMF forcefully inhibited monocyte binding to immobilised E-selectin by 55.7%. Furthermore, MMF significantly inhibited the upregulation of ICAM-1- and MHC-II-expression on monocytes stimulated with either lipopolysaccharide or interferon-gamma, whereas the expression of sLeX was not impaired. Toxic effects were excluded by propidium-iodide staining and measurement of fluorescein-diacetate metabolism.

CONCLUSION

MMF can downregulate important monocytic adhesion molecules and inhibits monocyte adhesion to endothelial cells, thus indicating that treatment with MMF could be beneficial after SCI.

SPONSORSHIP

This study was supported by the DFG (Ha 2721/1-3), the Paul und Ursula Klein-Stiftung and the Stiftung Friedrichsheim.

摘要

研究设计

霉酚酸酯（MMF）对分离的人单核细胞和内皮细胞作用的体外研究。

目的

血源性巨噬细胞在脊髓损伤（SCI）后继发性损伤的发展中起重要作用，有证据表明使用MMF等免疫抑制剂可减少单核细胞浸润和神经元损伤。

地点

德国美因河畔法兰克福大学骨科医院。

方法

研究了MMF对人单核细胞与人脐静脉内皮细胞（HUVEC）黏附、单核细胞与固定化E-选择素结合以及单核细胞细胞间黏附分子（ICAM）-1、唾液酸化路易斯X（sLeX）和主要组织相容性复合体（MHC）-II表达的影响。通过使用纯化和固定化的E-选择素融合蛋白检测单核细胞与E-选择素的结合。通过流式细胞术研究黏附分子的表达。

结果

用MMF（10微克/毫升）处理单核细胞后，单核细胞与HUVEC的结合显著降低了30.1%，而用MMF预处理HUVEC并未导致单核细胞黏附的显著变化。MMF强力抑制单核细胞与固定化E-选择素的结合达55.7%。此外，MMF显著抑制脂多糖或干扰素-γ刺激的单核细胞上ICAM-1和MHC-II表达的上调，而sLeX的表达未受损害。通过碘化丙啶染色和荧光素二乙酸代谢测量排除了毒性作用。