Sphingosylphosphorylcholine inhibits macrophage adhesion to vascular smooth muscle cells

Christiane Wirrig, Jenny S. McKean, Heather M. Wilson, Graeme F. Nixon

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3 Citations (Scopus)
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Inflammation in de-endothelialized arteries contributes to the development of cardiovascular diseases. The process that initiates this inflammatory response is the adhesion of monocytes/macrophages to exposed vascular smooth muscle cells, typically stimulated by cytokines such as tumour necrosis factor- (TNF). The aim of this study was to determine the effect of the sphingolipid sphingosylphosphorylcholine (SPC) on the interaction of monocytes/macrophages with vascular smooth muscle cells. Rat aortic smooth muscle cells and rat bone marrow-derived macrophages were co-cultured using an in vitro assay following incubation with sphingolipids to assess inter-cellular adhesion. We reveal that SPC inhibits the TNF-induced adhesion of macrophages to smooth muscle cells. This anti-adhesive effect was the result of SPC-induced changes to the smooth muscle cells (but not the macrophages) and was mediated, at least partly, via the sphingosine 1-phosphate receptor subtype 2. Lipid raft domains were also required. Although SPC did not alter expression or membrane distribution of the adhesion proteins intercellular adhesion molecule-1 and vascular cellular adhesion protein-1 in smooth muscle cells, SPC preincubation inhibited the TNF-induced increase in inducible nitric oxide synthase (NOS2) resulting in a subsequent decrease in nitric oxide production. Inhibiting NOS2 activation in smooth muscle cells led to a decrease in the adhesion of macrophages to smooth muscle cells. This study has therefore delineated a novel pathway which can inhibit the interaction between macrophages and vascular smooth muscle cells via SPC-induced repression of NOS2 expression. This mechanism could represent a potential drug target in vascular disease.
Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalBiochemical Pharmacology
Early online date8 Jul 2016
Publication statusPublished - 1 Sept 2016

Bibliographical note

CW and JSMcK were funded by British Heart Foundation studentships.


  • Vascular smooth muscle
  • Sphingolipids
  • Macrophage
  • Nitric oxide synthase
  • Lipid raft


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