Sulfated polysaccharides inhibit leukocyte rolling in rabbit mesentery venules

Before firm adhesion, leukocytes roll slowly along the walls of small venules at velocities ranging from 0.7 to 36% of mean blood flow velocity. To investigate the nature of the adhesive process underlying leukocyte rolling, synthetic (dextran sulfate) and naturally occurring sulfated polysaccharides (heparin, chondroitin sulfates, keratan sulfate, and heparan sulfate) were infused via glass micropipettes into the lumen of small venules (20-60 μm diam) of the rabbit mesentery. Leukocyte rolling was observed and quantified using both transmitted light and incident fluorescence intravital microscopy. Rolling leukocytes accounted for 27-80% of total leukocyte flux, exhibiting a wide range of individual velocities (0.01-0.84 mm/s) with a mean value of 4% of centerline velocity. Dextran sulfate (M(r) 500,000) inhibited leukocyte rolling very effectively [half-effective concentration (ED₅₀) ~ 10 μg/ml] and was able to almost completely abolish rolling at 500 μg/ml. Heparin (ED₅₀ ~ 50 μg/ml), chondroitin 6-sulfate C (ED₅₀ ~ 500 μg/ml), and heparan sulfate (ED₅₀ ~ 5 mg/ml) also reduced leukocyte rolling. At 5 mg/ml, chondroitin 4-sulfate B (dermatan sulfate) was marginally effective, but chondroitin 4-sulfate A and keratan sulfate were ineffective. The present data suggest that an adhesion receptor-ligand system distinct from the leukocyte integrins may be underlying transient leukocyte adhesion (rolling). Endothelial glycoproteins or proteoglycans containing sulfated side chains may be involved in mediating this adhesive process.