Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer

Article Article scientifique Article Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer eng 1999 author Lou Jinning 26933 author Gasche Yvan 32923 author Zheng Lei 106906 author Giroud Christine 22558 author Morel Philippe 22337 author Clements J author Ythier Arnaud André 562151 author Grau G E 1015-1025 10462039 0023-6837 Perivascular leukocyte infiltration into the central nervous system is characteristic of multiple sclerosis (MS) pathology. Interferon-beta (IFN-beta) has shown efficacy in the treatment of patients with MS, but the relevant mechanisms remain incompletely understood. In this study the effects of IFN-beta on leukocyte transendothelial migration were investigated using cells relevant to MS pathogenesis, namely human brain microvascular endothelial cells (HB-MVEC). Activated, but not resting leukocytes exhibited a high transendothelial migration capacity. HB-MVEC prestimulated with tumor necrosis factor (TNF) and IFN-gamma significantly promoted leukocyte transendothelial migration. IFN-beta inhibited the activated leukocyte transendothelial migration on TNF/IFN-gamma-activated HB-MVEC in a dose-dependent manner. A matrix metalloproteinase (MMP) inhibitor and monoclonal antibodies to lymphocyte function antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1), but not to very late antigen-4 or to vascular cell adhesion molecule-1 significantly inhibited the transendothelial migration of stimulated leukocytes, suggesting that this phenomenon involves the LFA-1/ICAM-1 interaction and MMP. However IFN-beta did not interfere with the binding of leukocytes to HB-MVEC unless IFN-beta was preincubated with leukocytes or added to HB-MVEC at the time of stimulation. Furthermore IFN-beta did not modulate the expression of adhesion molecules on either stimulated leukocytes or activated HB-MVEC, but partially reduced TNF and interleukin-1 production from stimulated leukocytes during coculture with HB-MVEC. Interestingly, in the presence of IFN-beta, a significant down-regulation of MMP-9 release from stimulated leukocytes was found, especially for the activated form of MMP-9. These results indicate that inhibition of leukocyte transendothelial migration is an important mechanism accounting for the beneficial effects of IFN-beta in the treatment MS patients. Brain/blood supply Cell Adhesion/drug effects Cell Movement/drug effects Cells, Cultured Endothelium, Vascular/cytology Humans Integrin alpha4beta1 Integrins/physiology Intercellular Adhesion Molecule-1/physiology Interferon-beta/pharmacology Interferon-gamma/pharmacology Interleukin-1/secretion Leukocytes/drug effects/physiology Matrix Metalloproteinase 9 Matrix Metalloproteinase Inhibitors Microcirculation/cytology Multiple Sclerosis/etiology/therapy Receptors, Lymphocyte Homing/physiology Tumor Necrosis Factor-alpha/secretion Vascular Cell Adhesion Molecule-1/physiology Dewey 617 57 Département de chirurgie 222 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 false 79 Chirurgie viscérale 104 1329 Chirurgie viscérale (HUG) 255 Groupe Gasche Yvan (Soins intensifs) 501 Laboratory investigation 79 8 147cccf8-5170-4407-85c8-8698fc57dd9b Article (Published version) Restricted 1999_lou_lab_invest.pdf 7353587 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences

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Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer	Laboratory investigation			1999	756	0

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Ythier, Arnaud André