TY - JOUR
T1 - GAS6 inhibits granulocyte adhesion to endothelial cells
AU - Avanzi, Gian Carlo
AU - Gallicchio, Margherita
AU - Bottarel, Flavia
AU - Gammaitoni, Loretta
AU - Cavalloni, Giuliana
AU - Buonfiglio, Donatella
AU - Bragardo, Manuela
AU - Bellomo, Giorgio
AU - Albano, Emanuele
AU - Fantozzi, Roberto
AU - Garbarino, Giovanni
AU - Varnum, Brian
AU - Aglietta, Massimo
AU - Saglio, Giuseppe
AU - Dianzani, Umberto
AU - Dianzani, Chiara
PY - 1998/4/1
Y1 - 1998/4/1
N2 - GAS6 is a ligand for the tyrosine kinase receptors Rse, Axl, and Mar, but its function is poorly understood. Previous studies reported that both GAS6 and Axl are expressed by vascular endothelial cells (EC), which play a key role in leukocyte extravasation into tissues during inflammation through adhesive interactions with these cells. The aim of this work was to evaluate the GAS6 effect on the adhesive function of EC. Treatment of EC with GAS6 significantly inhibited adhesion of polymorphonuclear cells (PMN) induced by phorbol 12-myristate 13-acetate (PMA), platelet-activating factor (PAF), thrombin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), but not that induced by FMLP and IL-8. GAS6 did not affect adhesion to resting EC. Titration experiments showed that high concentrations of GAS6 were needed to inhibit PMN adhesion and that inhibition was dose-dependent at the concentration range of 0.1 to 1 μg/mL. One possibility was that high concentrations were needed to overwhelm the affect of endogenous GAS6 produced by EC. In line with this possibility, treatment of resting EC with soluble Axl significantly potentiated PMN adhesion. Analysis of localization of GAS6 by confocal microscopy and cytofluorimetric analysis showed that it is concentrated along the plasma membrane in resting EC and treatment with PAF induces depletion and/or redistribution of the molecule. These data suggest that GAS6 functions as a physiologic antiinflammatory agent produced by resting EC and depleted when proinflammatory stimuli turn on the proadhesive machinery of EC.
AB - GAS6 is a ligand for the tyrosine kinase receptors Rse, Axl, and Mar, but its function is poorly understood. Previous studies reported that both GAS6 and Axl are expressed by vascular endothelial cells (EC), which play a key role in leukocyte extravasation into tissues during inflammation through adhesive interactions with these cells. The aim of this work was to evaluate the GAS6 effect on the adhesive function of EC. Treatment of EC with GAS6 significantly inhibited adhesion of polymorphonuclear cells (PMN) induced by phorbol 12-myristate 13-acetate (PMA), platelet-activating factor (PAF), thrombin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), but not that induced by FMLP and IL-8. GAS6 did not affect adhesion to resting EC. Titration experiments showed that high concentrations of GAS6 were needed to inhibit PMN adhesion and that inhibition was dose-dependent at the concentration range of 0.1 to 1 μg/mL. One possibility was that high concentrations were needed to overwhelm the affect of endogenous GAS6 produced by EC. In line with this possibility, treatment of resting EC with soluble Axl significantly potentiated PMN adhesion. Analysis of localization of GAS6 by confocal microscopy and cytofluorimetric analysis showed that it is concentrated along the plasma membrane in resting EC and treatment with PAF induces depletion and/or redistribution of the molecule. These data suggest that GAS6 functions as a physiologic antiinflammatory agent produced by resting EC and depleted when proinflammatory stimuli turn on the proadhesive machinery of EC.
UR - http://www.scopus.com/inward/record.url?scp=0032055167&partnerID=8YFLogxK
U2 - 10.1182/blood.v91.7.2334.2334_2334_2340
DO - 10.1182/blood.v91.7.2334.2334_2334_2340
M3 - Article
SN - 0006-4971
VL - 91
SP - 2334
EP - 2340
JO - Blood
JF - Blood
IS - 7
ER -