Regulation of human B-cell precursor adhesion to bone marrow stromal cells by cytokines that exert opposing effects on the expression of vascular cell adhesion molecule-1 (VCAM-1)
| Autor: | B N, Dittel, J B, McCarthy, E A, Wayner, T W, LeBien |
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| Rok vydání: | 1993 |
| Předmět: |
Adult
Lipopolysaccharides B-Lymphocytes Interleukins Immunology Vascular Cell Adhesion Molecule-1 Bone Marrow Cells Cell Biology Hematology Flow Cytometry Hematopoietic Stem Cells Biochemistry Recombinant Proteins Interferon-gamma Kinetics Fetus Antigens CD Bone Marrow Transforming Growth Factor beta Cell Adhesion Cytokines Humans Fibroblast Growth Factor 2 Cell Adhesion Molecules |
| Zdroj: | Blood. 81:2272-2282 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v81.9.2272.bloodjournal8192272 |
| Popis: | Self-renewal and differentiation of B-cell precursors is dependent on interactions with bone marrow (BM) stromal cells and associated extracellular matrix. We have recently developed an interleukin (IL)-7- dependent, BM-derived stromal cell culture that supports the growth of normal human B-cell precursors. In the current study, we have characterized the constitutive expression, cytokine-regulated expression, and function of adhesion molecules on BM stromal cells that are critical for adhesion of B-cell precursors. Flow cytometric analysis showed that cultured adult BM stromal cells expressed higher constitutive levels of vascular cell adhesion molecule (VCAM)-1 than intercellular adhesion molecule (ICAM)-1 (CD54). IL-1 beta upregulated VCAM-1 and CD54 in a dose-dependent manner, whereas IL-4 upregulated VCAM-1, but had no effect on CD54. In contrast, transforming growth factor (TGF)-beta decreased the level of BM stromal cell VCAM-1. Using an assay to measure the adhesion of 51Cr-labeled B-cell precursors to BM stromal cells, we observed a direct correlation between cytokine- regulated levels of VCAM-1 and the capacity of stromal cells to support the adhesion of B-cell precursors. Blocking studies using a panel of monoclonal antibodies (MoAb) showed that adhesion of B-cell precursors to untreated and cytokine-treated (IL-1 beta, IL-4) BM stromal cells was mediated by very late antigen (VLA)-4 (CD49d/CD29) and VCAM-1. Adhesion of B-cell precursors could also be enhanced by direct stimulation with MoAb to the CD29 subunit. Our collective results indicate that B-cell precursor/BM stromal cell adhesion is mediated by a VLA-4-VCAM-1 interaction, which in turn can be regulated at the level of the BM stromal cell by cytokines that specifically increase or decrease cell surface VCAM-1. |
| Databáze: | OpenAIRE |
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