Role of CD11/CD18 in shear rate-dependent leukocyte-endothelial cell interactions in cat mesenteric venules

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.