Inhibition of chemotactic motility and trans‐endothelial migration of human neutrophils by sphingosine 1‐phosphate

FEBS Letters

Kawa, Shigeyuki¹  Kimura, Satoshi¹  Hakomori, Sen-itiro¹  Igarashi, Yasuyuki¹ 

[1] The Biomembrane Institute and Department of Pathobiology, University of Washington, Seattle, WA 90104, USA

关键词: Sphingosine 1-phosphate;    Neutrophil motility;    Neutrophil migration;    CPAE;    cow pulmonary artery endothelial cell;    FCS;    fetal calf serum;    fMLP;    N-formyl-methionyl-leucyl-phenylalanine;    HUVEC;    human umbilical vein endothelial cell;    PKC;    protein kinase C;    PMA;    phorbol 12-myristate 13-acetate;    Sph-1-P;    sphingosine 1-phosphate;    TMS;    N;    N;    N-trimethylsphingosine;   

DOI  :  10.1016/S0014-5793(97)01516-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In previous studies, we reported that sphingosine 1-phosphate (Sph-1-P) inhibits the chemotactic motility of some cancer cell lines such as mouse melanoma cells, as well as human smooth muscle cells, at a very low concentration, as demonstrated by a transwell migration assay method (Proc. Natl. Acad. Sci. USA 89, 9698, 1992; J. Cell Biol. 130, 193, 1995). In this study, we investigated the effect of Sph-1-P on the chemotactic motility and invasiveness of human neutrophils, utilizing three different assay systems: (a) a transwell migration assay where IL-8 or fLMP was added as a chemotactic factor, (b) a phagokinetic assay with gold colloids, and (c) a trans-endothelial migration assay with human umbilical vein endothelial cells (HUVECs) plated on collagen layers. We found that among various sphingosine derivatives, Sph-1-P specifically inhibited the IL-8- or fLMP-induced chemotactic migration of neutrophils at concentrations below 1 μM. Phagokinetic activity of neutrophils was also suppressed by Sph-1-P, but more moderately than by the PKC inhibitory sphingosine analog, trimethylsphingosine. Finally, Sph-1-P inhibited trans-endothelial migration and invasiveness of neutrophils into HUVEC-covered collagen layers, whereas no effect on their adhesion to HUVECs was observed. These observations strongly suggest that Sph-1-P can act as a specific and effective motility regulator of human neutrophils, raising the possibility of future applications of Sph-1-P, or its analogs, as anti-inflammatory agents regulating invasive migration of neutrophils through endothelial layers at injured vascular sites.

【 授权许可】

Unknown