ABSTRACT Purpose: The acute phase protein, a1-acid glycoprotein, is expressed in the lung, and influences endothelial cell function. We asked whether it might regulate angiogenesis in @entity1 lung microvascular endothelia. MATERIALS AND METHODS: a1-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, @entity3209 -albumin, were tested. RESULTS: a1-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%. a1-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 @entity7 and @entity540 -driven migration but failed to inhibit chemotactic responsiveness. When a1-acid glycoprotein was added to preformed tubes, it provoked their almost immediate disassembly. As early as 15 minutes, it induced @entity5274 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 (14)C-albumin flux. CONCLUSION: a1-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.

a1-Acid glycoprotein disrupts capillary-like tube formation of XXXX lung microvascular endothelia.

@entity1 :: ('9606', 'Species') :: ['human'] @entity7 :: ('7422', 'Gene') :: ['vascular endothelial growth factor-A'] @entity540 :: ('2247', 'Gene') :: ['fibroblast growth factor-2'] @entity5274 :: ('MESH:D005184', 'Disease') :: ['tube network collapse'] @entity3209 :: ('CHEBI:36927', 'Chemical') :: ['(14)C']
@entity1 :: (9606,Species) :: ['human']
