Purpose: The acute phase protein, α1-acid glycoprotein, is expressed in the lung, and influences endothelial cell function. We asked whether it might regulate angiogenesis in human lung microvascular endothelia. Materials and Methods: α1-acid glycoprotein was isolated from human serum by HPLC ion exchange chromatography. Its effects on endothelial cell functions including capillary-like tube formation on Matrigel, migration in a wounding assay, chemotaxis in a modified Boyden chamber, adhesion, and transendothelial flux of the permeability tracer, 14C-albumin, were tested. Results: α1-acid glycoprotein dose-dependently inhibited capillary-like tube formation without loss of cell viability. At ≥0.50 mg/mL, it inhibited tube formation >70%, and at 0.75 mg/mL, >97%. α1-acid glycoprotein dose- and time-dependently restrained EC migration into a wound as early as 2 hours, and in washout studies, did so reversibly. It was inhibitory against vascular endothelial growth factor-A and fibroblast growth factor-2-driven migration but failed to inhibit chemotactic responsiveness. When α1-acid glycoprotein was added to preformed tubes, it provoked their almost immediate disassembly. As early as 15 minutes, it induced tube network collapse without endothelial cell-cell disruption. It exerted a biphasic effect on cell adhesion to the Matrigel substrate. At lower concentrations (0.05-0.25 mg/mL), it increased cell adhesion, whereas at higher concentrations (≥0.75 mg/mL) decreased adhesion. In contrast, it had no effect on transendothelial 14C-albumin flux. Conclusion: α1-acid glycoprotein, at concentrations found under physiological conditions, rapidly inhibits endothelial cell capillary-like tube formation that may be explained through diminished cell adhesion to the underlying matrix and/or reversibly decreased cell migration.

α1-acid glycoprotein disrupts capillary-like tube formation of human lung microvascular endothelia / A. Miranda-Ribera, A. Passaniti, F. Ceciliani, S.E. Goldblum. - In: EXPERIMENTAL LUNG RESEARCH. - ISSN 0190-2148. - 40:10(2014 Dec), pp. 507-519. [10.3109/01902148.2014.956945]

α1-acid glycoprotein disrupts capillary-like tube formation of human lung microvascular endothelia

A. Miranda-Ribera
Primo
;
F. Ceciliani
Penultimo
;
2014

Abstract

Purpose: The acute phase protein, α1-acid glycoprotein, is expressed in the lung, and influences endothelial cell function. We asked whether it might regulate angiogenesis in human lung microvascular endothelia. Materials and Methods: α1-acid glycoprotein was isolated from human serum by HPLC ion exchange chromatography. Its effects on endothelial cell functions including capillary-like tube formation on Matrigel, migration in a wounding assay, chemotaxis in a modified Boyden chamber, adhesion, and transendothelial flux of the permeability tracer, 14C-albumin, were tested. Results: α1-acid glycoprotein dose-dependently inhibited capillary-like tube formation without loss of cell viability. At ≥0.50 mg/mL, it inhibited tube formation >70%, and at 0.75 mg/mL, >97%. α1-acid glycoprotein dose- and time-dependently restrained EC migration into a wound as early as 2 hours, and in washout studies, did so reversibly. It was inhibitory against vascular endothelial growth factor-A and fibroblast growth factor-2-driven migration but failed to inhibit chemotactic responsiveness. When α1-acid glycoprotein was added to preformed tubes, it provoked their almost immediate disassembly. As early as 15 minutes, it induced tube network collapse without endothelial cell-cell disruption. It exerted a biphasic effect on cell adhesion to the Matrigel substrate. At lower concentrations (0.05-0.25 mg/mL), it increased cell adhesion, whereas at higher concentrations (≥0.75 mg/mL) decreased adhesion. In contrast, it had no effect on transendothelial 14C-albumin flux. Conclusion: α1-acid glycoprotein, at concentrations found under physiological conditions, rapidly inhibits endothelial cell capillary-like tube formation that may be explained through diminished cell adhesion to the underlying matrix and/or reversibly decreased cell migration.
Acute phase response; Angiogenesis; Endothelium; Orosomucoid; α1-acid glycoprotein
Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria
dic-2014
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/271316
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