Natalizumab treatment reduces endothelial activity in MS patients

被引：32

作者：

Millonig, Alban ^{[1
]}

Hegen, Harald ^{[1
]}

Di Pauli, Franziska ^{[1
]}

Ehling, Rainer ^{[1
]}

Gneiss, Claudia ^{[1
]}

Hoelzl, Martina ^{[1
]}

Kuenz, Bettina ^{[1
]}

Lutterotti, Andreas ^{[1
]}

Rudzki, Dagmar ^{[1
]}

Berger, Thomas ^{[1
]}

Reindl, Markus ^{[1
]}

Deisenhammer, Florian ^{[1
]}

机构：

[1] Innsbruck Med Univ, Dept Neurol, A-6020 Innsbruck, Austria

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2010年 / 227卷 / 1-2期

关键词：

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; SOLUBLE ADHESION MOLECULES; RELAPSING MULTIPLE-SCLEROSIS; ALPHA-CONVERTING ENZYME; INTERFERON-BETA; CELL-ADHESION; MONOCLONAL-ANTIBODIES; CONTROLLED TRIAL; VCAM-1; BLOOD;

D O I：

10.1016/j.jneuroim.2010.07.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Vascular cell adhesion molecule-1 a ligand for leukocyte very late activating antigen-4 is a key player in leukocyte extravasation in MS lesions. Natalizumab a monoclonal antibody against VLA-4 blocks this interaction. VCAM-1 and its soluble form are up-regulated during endothelial activation in MS. We investigated the effect of Natalizumab on sVCAM-1 and VLA-4 on circulating leukocytes in MS patients. Natalizumab reduced levels of sVCAM-1 compared to controls (256 vs. 597 ng/mL). This effect was sustained and only reversed in patients with neutralizing antibodies against Natalizumab. Correspondingly Natalizumab diminished VLA-4 on leukocyte subsets. Our findings indicate that Natalizumab reduces transmigration not only by blocking VLA-4 but also by down-regulating VCAM-1. (c) 2010 Elsevier B.V. All rights reserved.

引用

页码：190 / 194

页数：5

共 37 条

[1]

BROSNAN CF, 1995, NEUROLOGY, V516, pS16

[2] VLA-4 expression on peripheral blood lymphocytes is downregulated after treatment of multiple sclerosis with interferon beta [J].

Calabresi, PA ;

Pelfrey, CM ;

Tranquill, LR ;

Maloni, H ;

McFarland, HF .

NEUROLOGY, 1997, 49 (04) :1111-1116

[3] Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon beta-1b [J].

Calabresi, PA ;

Tranquill, LR ;

Dambrosia, JM ;

Stone, LA ;

Maloni, H ;

Bash, CN ;

Frank, JA ;

McFarland, HF .

ANNALS OF NEUROLOGY, 1997, 41 (05) :669-674

[4] T lymphocytes conditioned with Interferon β induce membrane and soluble VCAM on human brain endothelial cells [J].

Calabresi, PA ;

Prat, A ;

Biernacki, K ;

Rollins, J ;

Antel, JP .

JOURNAL OF NEUROIMMUNOLOGY, 2001, 115 (1-2) :161-167

[5] THE ADHESION MOLECULE AND CYTOKINE PROFILE OF MULTIPLE-SCLEROSIS LESIONS [J].

CANNELLA, B ;

RAINE, CS .

ANNALS OF NEUROLOGY, 1995, 37 (04) :424-435

[6] A comparative study of the relative bioavailability of different interferon beta preparations [J].

Deisenhammer, F ;

Mayringer, I ;

Harvey, J ;

Dilitz, E ;

Gasse, T ;

Stadlbauer, D ;

Reindl, M ;

Berger, T .

NEUROLOGY, 2000, 54 (11) :2055-2060

[7] Neutralizing Antibodies to Interferon-β and other Immunological Treatments for Multiple Sclerosis Prevalence and Impact on Outcomes [J].

Deisenhammer, Florian .

CNS DRUGS, 2009, 23 (05) :379-396

[8] The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms [J].

Engelhardt, B ;

Ransohoff, RM .

TRENDS IN IMMUNOLOGY, 2005, 26 (09) :485-495

[9] Stimulated shedding of vascular cell adhesion molecule 1 (VCAM-1) is mediated by tumor necrosis factor-α-converting enzyme (ADAM 17) [J].

Garton, KJ ;

Gough, PJ ;

Philalay, J ;

Wille, PT ;

Blobel, CP ;

Whitehead, RH ;

Dempsey, PJ ;

Raines, EW .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (39) :37459-37464

[10] Longitudinal study of soluble adhesion molecules in multiple sclerosis: Correlation with gadolinium enhanced magnetic resonance Imaging [J].

Giovannoni, G ;

Lai, M ;

Thorpe, J ;

Kidd, D ;

Chamoun, V ;

Thompson, AJ ;

Miller, DH ;

Feldmann, M ;

Thompson, EJ .

NEUROLOGY, 1997, 48 (06) :1557-1565

← 1 2 3 4 →