Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 43-50 |
| Number of pages | 8 |
| Journal | Biochemical Pharmacology |
| Volume | 115 |
| Early online date | 8 Jul 2016 |
| DOIs | |
| Publication status | Published - 1 Sep 2016 |
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Keywords
- Vascular smooth muscle
- Sphingolipids
- Macrophage
- Nitric oxide synthase
- Lipid raft
Cite this
Sphingosylphosphorylcholine inhibits macrophage adhesion to vascular smooth muscle cells. / Wirrig, Christiane; McKean, Jenny S.; Wilson, Heather M.; Nixon, Graeme F.
In: Biochemical Pharmacology, Vol. 115, 01.09.2016, p. 43-50.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Sphingosylphosphorylcholine inhibits macrophage adhesion to vascular smooth muscle cells
AU - Wirrig, Christiane
AU - McKean, Jenny S.
AU - Wilson, Heather M.
AU - Nixon, Graeme F.
N1 - Acknowledgement CW and JSMcK were funded by British Heart Foundation studentships.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - Vascular smooth muscle
KW - Sphingolipids
KW - Macrophage
KW - Nitric oxide synthase
KW - Lipid raft
U2 - 10.1016/j.bcp.2016.07.004
DO - 10.1016/j.bcp.2016.07.004
M3 - Article
VL - 115
SP - 43
EP - 50
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
ER -