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

FEBS Lett. 1997 Dec 29;420(2-3):196-200. doi: 10.1016/s0014-5793(97)01516-0.

Abstract

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 microM. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Ceramides / pharmacology
  • Chemotaxis / drug effects*
  • Enzyme Inhibitors / pharmacology
  • Gold Colloid
  • Humans
  • Inflammation / metabolism
  • Interleukin-8 / pharmacology
  • Lysophospholipids*
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils
  • Phagocytosis
  • Protein Kinase C / antagonists & inhibitors
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Umbilical Cord

Substances

  • Ceramides
  • Enzyme Inhibitors
  • Gold Colloid
  • Interleukin-8
  • Lysophospholipids
  • N,N,N-trimethylsphingosine
  • sphingosine 1-phosphate
  • N-Formylmethionine Leucyl-Phenylalanine
  • Protein Kinase C
  • Sphingosine