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Generation of Shear Adhesion Map Using SynVivo Synthetic Microvascular Networks
Published on: May 25, 2014
Role of CD11/CD18 in shear rate-dependent leukocyte-endothelial cell interactions in cat mesenteric venules
1School of Physiology & Pharmacology, University of New South Wales, Kensington, Australia.
Insights
Leukocyte rolling velocity and adherence in cats depend on shear stress. Lower shear rates increase adherence, especially in venules, and CD18 antibodies reduce this interaction.
Area of Science:
- Microcirculation research
- Leukocyte-endothelial interactions
- Hemodynamics
Background:
- Leukocyte rolling and adherence are critical in inflammation and immune responses.
- Understanding the factors influencing these processes, such as shear stress, is vital for therapeutic development.
Purpose of the Study:
- To investigate the relationship between shear rate, shear stress, leukocyte rolling velocity, and leukocyte adherence in cat mesenteric microvessels.
- To determine the role of CD18 in mediating leukocyte-endothelial interactions under varying flow conditions.
Main Methods:
- In vivo microscopy was employed to observe leukocyte behavior in cat mesenteric venules and arterioles.
- Shear rate was manipulated by graded arterial loop occlusion.
- Leukocyte rolling velocity and adherence were quantified.
- The effect of CD18-specific antibody (mAb) IB4 was assessed.
Main Results:
- Leukocyte rolling velocity linearly decreased with red blood cell velocity.
- Leukocyte adherence increased significantly at lower shear stress, particularly below 50 microns/s.
- Venules exhibited higher leukocyte adherence than arterioles at similar low shear rates.
- mAb IB4 treatment increased leukocyte rolling velocity and largely inhibited adherence, indicating a CD18-dependent mechanism.
Conclusions:
- Shear rate and stress significantly influence leukocyte rolling and adherence in microvessels.
- Venules show a greater propensity for leukocyte adhesion than arterioles, not solely explained by shear rate differences.
- CD18 plays a crucial role in mediating leukocyte-endothelial adhesion in this model.
Abstract:
In vivo microscopy was used to assess the relationships among shear rate (and shear stress), leukocyte rolling velocity, and leukocyte adherence in a cat mesentery preparation. Shear rate in individual venules and arterioles of 25-35 microns diameter were varied over a wide range by graded occlusion of an arterial loop. There was a linear decline in leukocyte rolling velocity (Vwbc) as red cell velocity (Vrbc) was reduced. The ratio Vwbc/Vrbc remained constant despite variations in shear stress from 5-25 dyn/cm2. A reduction in shear stress was associated with an increased leukocyte adherence, particularly when Vwbc was reduced below 50 microns/s. Reduction in wall shear rate below 500 s-1 in arterioles allowed 1-3 leukocytes to adhere per 100 microns length of vessel, while venules exposed to the same shear rates had 5-16 adherent leukocytes. In arterioles, leukocyte rolling was only observed at low shear rates. At shear rates less than 250 s-1 leukocyte rolling velocity was faster in arterioles than venules, and the ratio Vwbc/Vrbc for arterioles was 0.08 +/- 0.02, which was fourfold higher than the ratio obtained in venules at similar shear rates. Pretreatment with the CD18-specific antibody (mAb) IB4 increased leukocyte rolling velocity in venules by approximately 20 microns/s at red cell velocities below 2,000 microns/s. mAb IB4 largely prevented the leukocyte adherence to arterioles and venules, and increased the ratio Vwbc/Vrbc observed in venules at low shear elicit a CD18-dependent adhesive interaction between leukocytes and microvascular endothelium, and that differences in shear rates cannot explain the greater propensity for leukocyte rolling and adhesion in venules than arterioles.
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