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The suppressive effect of sphingosine 1-phosphate on monocyte-endothelium adhesion may be mediated by the rearrangement of the endothelial integrins alpha(5)beta(1) and alpha(v)beta(3).
J Thromb Haemost. 2007 Jun; 5(6):1292-301.JT

Abstract

BACKGROUND

Sphingosine 1-phosphate (S1P), known to play important roles in vascular biology, is a bioactive lysophospholipid mediator that maintains endothelial integrity via its cell-surface receptors (S1Ps). In this in vitro study, we aimed to examine the role of S1P in monocyte-endothelium adhesion, which is an important event in the pathophysiology of atherosclerosis.

METHODS AND RESULTS

S1P pretreatment of human umbilical vein endothelial cells (ECs), but not U937 cells, effectively suppressed U937-EC adhesion independently from the expression of adhesion molecules, namely ICAM-1, VCAM-1, and E-selectin. This S1P-induced suppressive effect was inhibited by the blockage of S1P(1) and S1P(3) receptors and the specific inhibitors of G(i) protein, Src family proteins, phosphatidylinositol 3-kinase, and Rac1, indicating involvement of these key downstream pathways. Moreover, the RGD peptide and antibodies, which neutralize adhesion via alpha(5)beta(1) and alpha(v)beta(3), effectively inhibited U937-EC adhesion with a degree similar to S1P pretreatment. Both an adhesion assay and flow-cytometric analysis demonstrated that U937 cells adhered through integrins alpha(5)beta(1) and alpha(v)beta(3) expressed on the apical surface of monolayer ECs, and S1P shifted the localization of these integrins from the apical surface to the basal surface.

CONCLUSIONS

From the present results, we propose that S1P may contribute to the maintenance of vascular integrity and the regulation of atherogenesis through the rearrangement of endothelial integrins.

Authors+Show Affiliations

Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17403093

Citation

Aoki, S, et al. "The Suppressive Effect of Sphingosine 1-phosphate On Monocyte-endothelium Adhesion May Be Mediated By the Rearrangement of the Endothelial Integrins Alpha(5)beta(1) and Alpha(v)beta(3)." Journal of Thrombosis and Haemostasis : JTH, vol. 5, no. 6, 2007, pp. 1292-301.
Aoki S, Yatomi Y, Shimosawa T, et al. The suppressive effect of sphingosine 1-phosphate on monocyte-endothelium adhesion may be mediated by the rearrangement of the endothelial integrins alpha(5)beta(1) and alpha(v)beta(3). J Thromb Haemost. 2007;5(6):1292-301.
Aoki, S., Yatomi, Y., Shimosawa, T., Yamashita, H., Kitayama, J., Tsuno, N. H., Takahashi, K., & Ozaki, Y. (2007). The suppressive effect of sphingosine 1-phosphate on monocyte-endothelium adhesion may be mediated by the rearrangement of the endothelial integrins alpha(5)beta(1) and alpha(v)beta(3). Journal of Thrombosis and Haemostasis : JTH, 5(6), 1292-301.
Aoki S, et al. The Suppressive Effect of Sphingosine 1-phosphate On Monocyte-endothelium Adhesion May Be Mediated By the Rearrangement of the Endothelial Integrins Alpha(5)beta(1) and Alpha(v)beta(3). J Thromb Haemost. 2007;5(6):1292-301. PubMed PMID: 17403093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The suppressive effect of sphingosine 1-phosphate on monocyte-endothelium adhesion may be mediated by the rearrangement of the endothelial integrins alpha(5)beta(1) and alpha(v)beta(3). AU - Aoki,S, AU - Yatomi,Y, AU - Shimosawa,T, AU - Yamashita,H, AU - Kitayama,J, AU - Tsuno,N H, AU - Takahashi,K, AU - Ozaki,Y, PY - 2007/4/4/pubmed PY - 2007/7/21/medline PY - 2007/4/4/entrez SP - 1292 EP - 301 JF - Journal of thrombosis and haemostasis : JTH JO - J Thromb Haemost VL - 5 IS - 6 N2 - BACKGROUND: Sphingosine 1-phosphate (S1P), known to play important roles in vascular biology, is a bioactive lysophospholipid mediator that maintains endothelial integrity via its cell-surface receptors (S1Ps). In this in vitro study, we aimed to examine the role of S1P in monocyte-endothelium adhesion, which is an important event in the pathophysiology of atherosclerosis. METHODS AND RESULTS: S1P pretreatment of human umbilical vein endothelial cells (ECs), but not U937 cells, effectively suppressed U937-EC adhesion independently from the expression of adhesion molecules, namely ICAM-1, VCAM-1, and E-selectin. This S1P-induced suppressive effect was inhibited by the blockage of S1P(1) and S1P(3) receptors and the specific inhibitors of G(i) protein, Src family proteins, phosphatidylinositol 3-kinase, and Rac1, indicating involvement of these key downstream pathways. Moreover, the RGD peptide and antibodies, which neutralize adhesion via alpha(5)beta(1) and alpha(v)beta(3), effectively inhibited U937-EC adhesion with a degree similar to S1P pretreatment. Both an adhesion assay and flow-cytometric analysis demonstrated that U937 cells adhered through integrins alpha(5)beta(1) and alpha(v)beta(3) expressed on the apical surface of monolayer ECs, and S1P shifted the localization of these integrins from the apical surface to the basal surface. CONCLUSIONS: From the present results, we propose that S1P may contribute to the maintenance of vascular integrity and the regulation of atherogenesis through the rearrangement of endothelial integrins. SN - 1538-7933 UR - https://www.unboundmedicine.com/medline/citation/17403093/The_suppressive_effect_of_sphingosine_1_phosphate_on_monocyte_endothelium_adhesion_may_be_mediated_by_the_rearrangement_of_the_endothelial_integrins_alpha_5_beta_1__and_alpha_v_beta_3__ DB - PRIME DP - Unbound Medicine ER -