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 |
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Erscheinungsjahr: |
1995 |
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Erschienen: |
1995 |
Enthalten in: |
Zur Gesamtaufnahme - volume:154 |
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Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 154(1995), 4 vom: 15. Feb., Seite 1888-99 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Rosenman, S J [VerfasserIn] |
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Anmerkungen: |
Date Completed 27.02.1995 Date Revised 21.11.2008 published: Print Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM075068710 |
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041 | |a eng | ||
100 | 1 | |a Rosenman, S J |e verfasserin |4 aut | |
245 | 1 | 0 | |a Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines |
264 | 1 | |c 1995 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
338 | |a Band |b nc |2 rdacarrier | ||
500 | |a Date Completed 27.02.1995 | ||
500 | |a Date Revised 21.11.2008 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
650 | 7 | |a Cell Adhesion Molecules |2 NLM | |
650 | 7 | |a Cytokines |2 NLM | |
650 | 7 | |a HLA-DR Antigens |2 NLM | |
650 | 7 | |a Interleukin-1 |2 NLM | |
650 | 7 | |a Neoplasm Proteins |2 NLM | |
650 | 7 | |a RNA, Messenger |2 NLM | |
650 | 7 | |a RNA, Neoplasm |2 NLM | |
650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
650 | 7 | |a Vascular Cell Adhesion Molecule-1 |2 NLM | |
650 | 7 | |a Interleukin-4 |2 NLM | |
650 | 7 | |a 207137-56-2 |2 NLM | |
650 | 7 | |a Interferon-gamma |2 NLM | |
650 | 7 | |a 82115-62-6 |2 NLM | |
700 | 1 | |a Shrikant, P |e verfasserin |4 aut | |
700 | 1 | |a Dubb, L |e verfasserin |4 aut | |
700 | 1 | |a Benveniste, E N |e verfasserin |4 aut | |
700 | 1 | |a Ransohoff, R M |e verfasserin |4 aut | |
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773 | 1 | 8 | |g volume:154 |g year:1995 |g number:4 |g day:15 |g month:02 |g pages:1888-99 |
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