TY -JOUR
AU -Hsinyu Lee
TI -Enhancement of Human Endothelial Cell Adhesion to Type I Collagen by Lysophosphatidic Acid (LPA) and Sphingosine-1-Phosphate (S1P)
PY -2004
DA -0000-00-00
JO -Taiwania
VL -49
IS -2
SP -67
EP -79
UR -https://taiwania.ntu.edu.tw/abstract/2
AB -The diverse cellular effects of lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are transduced by two structurally homologous subfamilies of G protein-coupled
receptors, which are encoded by endothelial differentiation genes (Edg Rs). Human umbilical cord vein endothelial cells (HUVECs) express Edg Rs for LPA (Edg2) and S1P (Edg1 and 3), which transduce signals for migration of HUVECs through micropore filters coated with type I collagen. Since activation of integrins is essential for optimal migration of endothelial cells, we now examine the capacity of LPA and S1P to augment integrin mediation of endothelial cell binding to type I collagen. Lysophospholipid enhancement of HUVEC adhesion to type I collagen is detectable within 20 minutes. Enhancement of adhesion by both LPA and S1P is significant at 50 nM and optimal at 5µM. Pertussis toxin (PTx), a specific inhibitor of Gi, and C3 exotoxin, a specific inhibitor of Rho, both suppress LPA and S1P enhancement of HUVEC adhesion. In contrast, PD98059, which blocks MAP kinase kinase (MEK), and wortmannin, which inhibits phosphatidylinositol 3-kinase (PI3K), had no effect on LPA- or S1P-enhancement of HUVEC adhesion. Neutralizing monoclonal antibodies specific for α2 and β1 integrin chains, concomitantly decrease LPA and S1P enhancement of HUVEC adhesion to type I collagen. LPA and S1P thus promote type I collagen-dependent adhesion and migration of HUVECs by recruiting α2 and β1 integrin through both Gi and Rho pathways. Integrin α2/β1 therefore appears to be critical on the effects of LPA and S1P on endothelial cell physiology.
DO -10.6165/tai.2004.49(2).67