Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo

Giorgio Zauli, Federica Corallini, Fleur Bossi, Fabio Fischetti, Paolo Durigutto, Claudio Celeghini, Francesco Tedesco, Paola Secchiero

Research output: Contribution to journalArticle

Abstract

Recombinant osteoprotegerin (OPG) promoted the adhesion of both primary polymorphonuclear neutrophils (PMNs) and leukemic HL60 cells to endothelial cells. Leukocyte/endothelial cell adhesion was promoted by short (peak at 1 hour) preincubation of either endothelial cells or PMNs with OPG, and the peak of proadhesive activity was observed in the same range of OPG concentrations detected in the sera of patients affected by cardiovascular diseases. Although the cognate high-affinity ligands for OPG, membrane receptor activator of nuclear factor-κB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were detected at significant levels on both PMNs and HL60 cells, they were not expressed on the surface of endothelial cells. However, preincubation of OPG with heparin abrogated its proadhesive activity, whereas pretreatment of endothelial cells with chondroitinase plus heparinases significantly decreased the proadhesive activity of OPG. Taken together, these findings suggest the involvement of both the ligand binding and the N-terminal heparin-binding domains of OPG in mediating its pro-adhesive activity. The relevance of these in vitro findings was underscored by in vivo experiments, in which the topical administration of recombinant OPG increased leukocyte rolling and adhesion to rat mesenteric postcapillary venules. Our data suggest that a pathological increase of OPG serum levels might play an important role in promoting leukocyte/endothelial cell adhesion.

Original languageEnglish
Pages (from-to)536-543
Number of pages8
JournalBlood
Volume110
Issue number2
DOIs
Publication statusPublished - Jul 15 2007

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Osteoprotegerin
Endothelial cells
Leukocytes
Adhesion
Endothelial Cells
Neutrophils
HL-60 Cells
Cell adhesion
Ligands
Cell Adhesion
Heparin
Chondroitinases and Chondroitin Lyases
Leukocyte Rolling
RANK Ligand
Topical Administration
Venules
In Vitro Techniques
Cytoplasmic and Nuclear Receptors
Serum
Adhesives

ASJC Scopus subject areas

  • Hematology

Cite this

Zauli, G., Corallini, F., Bossi, F., Fischetti, F., Durigutto, P., Celeghini, C., ... Secchiero, P. (2007). Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo. Blood, 110(2), 536-543. https://doi.org/10.1182/blood-2007-01-068395

Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo. / Zauli, Giorgio; Corallini, Federica; Bossi, Fleur; Fischetti, Fabio; Durigutto, Paolo; Celeghini, Claudio; Tedesco, Francesco; Secchiero, Paola.

In: Blood, Vol. 110, No. 2, 15.07.2007, p. 536-543.

Research output: Contribution to journalArticle

Zauli, G, Corallini, F, Bossi, F, Fischetti, F, Durigutto, P, Celeghini, C, Tedesco, F & Secchiero, P 2007, 'Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo', Blood, vol. 110, no. 2, pp. 536-543. https://doi.org/10.1182/blood-2007-01-068395
Zauli G, Corallini F, Bossi F, Fischetti F, Durigutto P, Celeghini C et al. Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo. Blood. 2007 Jul 15;110(2):536-543. https://doi.org/10.1182/blood-2007-01-068395
Zauli, Giorgio ; Corallini, Federica ; Bossi, Fleur ; Fischetti, Fabio ; Durigutto, Paolo ; Celeghini, Claudio ; Tedesco, Francesco ; Secchiero, Paola. / Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo. In: Blood. 2007 ; Vol. 110, No. 2. pp. 536-543.
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