Fluid shear stress suppresses ICAM-1-mediated transendothelial migration of leukocytes in coculture model
Naoya Sakamoto1, Yosuke Ueki2, Masaki Oi2
1Graduate School of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo, 192-0397, Japan.
Insights
Fluid shear stress reduces leukocyte migration to arterial endothelial cells. Smooth muscle cells increase leukocyte adhesion via intercellular adhesion molecule-1 (ICAM-1) in static conditions, but shear stress counteracts this effect.
Area of Science:
- Cardiovascular Biology
- Atherosclerosis Research
- Cellular and Molecular Medicine
Background:
- Leukocyte adhesion and migration to arterial endothelial cells (ECs) are early indicators of atherogenesis.
- These processes are influenced by blood flow conditions and cell-cell interactions, including those with vascular smooth muscle cells (SMCs).
Purpose of the Study:
- To investigate the impact of fluid shear stress on leukocyte transendothelial migration.
- To examine the role of a co-culture model (CM) of ECs and SMCs in leukocyte migration.
Main Methods:
- A co-culture model (CM) comprising human umbilical ECs, SMCs, collagen type I, and a porous membrane was utilized.
- The CM was exposed to fluid shear stress (1.5 Pa for 24 hours).
- Leukocyte migration was quantified using confocal laser scanning microscopy after seeding leukocytes on the EC surface.
Main Results:
- Leukocyte migration was significantly higher in the static co-culture model compared to static EC monoculture.
- Exposure to fluid shear stress significantly reduced leukocyte migration under co-culture conditions.
- Static co-culture conditions showed increased expression of intercellular adhesion molecule-1 (ICAM-1) on ECs.
Conclusions:
- Vascular smooth muscle cell-derived factors may enhance intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells.
- This enhanced ICAM-1 expression in static co-culture conditions promotes leukocyte migration.
- Fluid shear stress counteracts the pro-migratory effect of SMCs on leukocytes in this model.
Abstract:
The adhesion and migration of leukocytes to arterial endothelial cells (ECs), one of the indicators of early atherogenesis, is believed to be correlated with the blood flow conditions and interactions between vascular cells including vascular smooth muscle cells (SMCs). In this study, we investigated the effect of fluid shear stress on the transendothelial migration of leukocytes in a coculture model (CM) composed of human umbilical ECs and SMCs, a layer of collagen type I, and a porous membrane. Following exposure to a fluid shear stress of 1.5 Pa for 24 h, human mononuclear leukocytes were seeded on the EC surface and cultured for 1 h. Leukocytes migrating across the EC layer were observed by confocal laser scanning microscopy. The number of migrating leukocytes in the statically cultured CM was significantly larger than that in the static EC monoculture model. The exposure to the shear stress significantly decreased the leukocyte migration induced by the coculture condition. In the static CM, fluorescence staining and Western blotting showed a higher expression of intercellular adhesion molecule-1 (ICAM-1) of ECs. These results indicate that SMC-derived bioactive soluble factors may stimulate the ICAM-1 expression of cocultured ECs, possibly leading to leukocyte migration into the subendothelial space.
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