Granulocyte-Macrophage Colony-Stimulating Factor Regulates the Functional Adhesive State of Very Late Antigen-4 Expressed by Eosinophils

K. L.Paul Sung, Li Yang, Mariano Elices, Gang Jin, P. Sriramarao, David H. Broide

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

As very late antigen-4 (VLA-4) can exist in different functional states, we have sought to determine whether a cytokine expressed by inflamed endothelium (i.e., granulocyte-macrophage CSF (GM-CSF)) could regulate the functional state of VLA-4 expressed by eosinophils. Using a micropipette single cell adhesion assay able to measure the strength of adhesion forces, eosinophils exhibited low levels of basal adhesion to unstimulated endothelium (separation force, 0.022 ± 0.003 mdynes). In contrast, individual eosinophils bound to IL-1β-stimulated endothelium (0.49 ± 0.02 mdynes), TNF-stimulated endothelium (0.62 ± 0.05 mdynes), or IL-4-stimulated endothelium (0.11 ± 0.01 mdynes) with increased avidity as assessed by separation force. Eosinophil binding to IL-4-stimulated endothelium was significantly inhibited by neutralizing Abs to either vascular cell adhesion molecule (VCAM) or VLA-4. The strength of eosinophil adhesion to VCAM (0.31 ± 0.02 mdynes) or to connecting segment-1 (CS-1) (0.18 mdynes) was greater than the strength of eosinophil adhesion to unstimulated endothelium (0.02 mdynes), but was less than the strength of eosinophil adhesion to IL-1β-stimulated endothelium (0.49 ± 0.02 mdynes). After incubating eosinophils for 30 min with GM-CSF, the mean adhesion strength of eosinophils to CS-1 and VCAM increased significantly by 84 and 54%, respectively, compared with that of controls. This increased binding of eosinophils to VCAM or CS-1 was not due to alterations in VLA-4 receptor number (assessed by FACS analysis) or alterations in VLA-4 receptor distribution (assessed by confocal microscopy). These studies suggest that endothelial-derived cytokines such as GM-CSF have the potential to alter the functional state of eosinophil-expressed VLA-4 from a low affinity state to a high affinity state.

Original languageEnglish (US)
Pages (from-to)919-927
Number of pages9
JournalJournal of Immunology
Volume158
Issue number2
StatePublished - Jan 15 1997

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