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

[21] Brief report - Progressive multifocal leukoencephalopathy in a patient treated with natalizumab [J].

Langer-Gould, A ;

Atlas, SW ;

Green, AJ ;

Bollen, AW ;

Pelletier, D .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (04) :375-381

[22] α4 Integrin/FN-CS1 mediated leukocyte adhesion to brain microvascular endothelial cells under flow conditions [J].

Man, Shumei ;

Tucky, Barbara ;

Bagheri, Nika ;

Li, Xiaolong ;

Kochar, Rabina ;

Ransohoff, Richard M. .

JOURNAL OF NEUROIMMUNOLOGY, 2009, 210 (1-2) :92-99

[23] Influence of IFN-β1b (Betaferon) on cytokine mRNA profiles in blood mononuclear cells and plasma levels of soluble VCAM-1 in multiple sclerosis [J].

Matusevicius, D ;

Kivisakk, P ;

Navikas, V ;

Tian, WZ ;

Soderstrom, M ;

Fredrikson, S ;

Link, H .

EUROPEAN JOURNAL OF NEUROLOGY, 1998, 5 (03) :265-275

[24] A controlled trial of natalizumab for relapsing multiple sclerosis. [J].

Miller, DH ;

Khan, OA ;

Sheremata, WA ;

Blumhardt, LD ;

Rice, GPA ;

Libonati, MA ;

Willmer-Hulme, AJ ;

Dalton, CM ;

Miszkiel, KA ;

O'Connor, PW .

NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (01) :15-23

[25] Mitochondrial Reactive Oxygen Species Mediate GPCR-induced TACE/ADAM17-dependent Transforming Growth Factor-α Shedding [J].

Myers, Timothy J. ;

Brennaman, Leann H. ;

Stevenson, Mary ;

Higashiyama, Shigeki ;

Russell, William E. ;

Lee, David C. ;

Sunnarborg, Susan Wohler .

MOLECULAR BIOLOGY OF THE CELL, 2009, 20 (24) :5236-5249

[26]

OPPERMANN K, 2009, MULT SCLER, V15, P133

[27] A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis [J].

Polman, CH ;

O'Connor, PW ;

Havrdova, E ;

Hutchinson, M ;

Kappos, L ;

Miller, DH ;

Phillips, JT ;

Lublin, FD ;

Giovannoni, G ;

Wajgt, A ;

Toal, M ;

Lynn, F ;

Panzara, MA ;

Sandrock, AW .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (09) :899-910

[28] Soluble adhesion molecules (sVCAM-1 and sICAM-1) in cerebrospinal fluid and serum correlate with MRI activity in multiple sclerosis [J].

Rieckmann, P ;

Altenhofen, B ;

Riegel, A ;

Baudewig, J ;

Felgenhauer, K .

ANNALS OF NEUROLOGY, 1997, 41 (03) :326-333

[29] The erbB family: Targets for therapeutic development against cancer and therapeutic strategies using monoclonal antibodies and tyrosine kinase inhibitors [J].

Rowinsky, EK .

ANNUAL REVIEW OF MEDICINE, 2004, 55 :433-457

[30] Neutrophil elastase induces MUC5AC mucin production in human airway epithelial cells via a cascade involving protein kinase C, reactive oxygen species, and TNF-α-converting enzyme [J].

Shao, MXG ;

Nade, JA .

JOURNAL OF IMMUNOLOGY, 2005, 175 (06) :4009-4016

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