Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines

Astrocytes in the central nervous system (CNS) associate intimately with vascular endothelial cells and are integral to the blood-brain barrier (BBB). Leukocyte transmigration across the BBB is a cardinal feature of CNS inflammation, as observed in experimental autoimmune encephalomyelitis, and very late antigen-4 (VLA-4)/vascular cell adhesion molecule-1 (VCAM-1) interactions have recently been proposed as essential for this process. VCAM-1 expression by astrocytes was recently reported. We addressed the regulation of VCAM-1 expression by inflammatory cytokines in primary human astrocytes and two human astrocytoma cell lines. Astrocytoma cells up-regulated surface VCAM-1 expression in response to cytokines in the following order: IFN-gamma plus TNF-alpha > IFN-gamma plus IL-1 beta > TNF-alpha > IFN-gamma. Cytokine-activated astrocytoma cells expressed 7-domain VCAM-1, as indicated by accumulation of 3.2-kb VCAM-1 mRNA and immunoprecipitation of a 100-kDa protein with anti-VCAM-1 mAb. Lymphoblast adhesion to cytokine-activated astrocytoma cell monolayers was significantly blocked by mAb specific for VCAM-1 and VLA-4, indicating that astrocytoma cell VCAM-1 was functional. Astrocytoma cell expression of VCAM-1 could be a constituent of the astrocyte phenotype. To support this possibility, we demonstrated that cytokine-treated adult human and rat primary astrocytes expressed VCAM-1, and the rank order of cytokine potency for VCAM-1 induction in primary and neoplastic astrocytes was strikingly similar. This is the first documentation of VCAM-1 expression by adult human astrocytes. Expression of VCAM-1 by astrocytes at the BBB could play a role in mononuclear leukocyte entry into the CNS.

Medienart:

Artikel

Erscheinungsjahr:

1995

Erschienen:

1995

Enthalten in:

Zur Gesamtaufnahme - volume:154

Enthalten in:

Journal of immunology (Baltimore, Md. : 1950) - 154(1995), 4 vom: 15. Feb., Seite 1888-99

Sprache:

Englisch

Beteiligte Personen:

Rosenman, S J [VerfasserIn]
Shrikant, P [VerfasserIn]
Dubb, L [VerfasserIn]
Benveniste, E N [VerfasserIn]
Ransohoff, R M [VerfasserIn]

Themen:

207137-56-2
82115-62-6
Cell Adhesion Molecules
Cytokines
HLA-DR Antigens
Interferon-gamma
Interleukin-1
Interleukin-4
Journal Article
Neoplasm Proteins
RNA, Messenger
RNA, Neoplasm
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1

Anmerkungen:

Date Completed 27.02.1995

Date Revised 21.11.2008

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM075068710