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Inhibition of leukocyte rolling in venules by protamine and sulfated
polysaccharides
GJ Tangelder and KE Arfors
La Jolla Institute for Experimental Medicine.
Intravital video microscopy was used to investigate leukocyte margination
in 80 mesenteric venules (19 to 54 microns) of 50 anesthetized rabbits.
After intravenous (IV) bolus injection, sulfated polysaccharides reduced in
a reversible and dose-dependent way the number of leukocytes rolling slowly
along the venular wall. The presence of sulfate groups is essential because
other negatively charged or neutral polysaccharides had no effect. It was
not caused by an increase in RBC velocity or chelation of divalent cations.
Inhibition by sulfated dextrans (n = 7) was independent of molecular weight
(mol wt 13,000 to 500,000) but was influenced by the average number of
sulfate groups per monosaccharide. With substitution 0.13, the
90%-inhibition dose was 104 mg/kg, with 0.7 it was 56 mg/kg, and between
substitution 1 and 2 it ranged from 20 to 23 mg/kg. At 100 mg/kg, plasma
concentration was 0.6 to 0.7 mg/mL. Xylan sulfate (mol wt 6,000,
substitution 1.8) gave 90% inhibition at 11 mg/kg, and heparin gave 90%
inhibition at 97 mg/kg. Duration of inhibition (0.5 to 2 hours) depended on
mol wt and appeared to be related to plasma clearance. Because protamine
also inhibited rolling (12 mg/kg; less than 10 minutes), we propose that
repetitive formation and breakup of ionic bonds between sulfate groups and
positively charged amino acids is involved in leukocyte rolling. During
inhibition of rolling, systemic lymphocyte/monocyte levels appeared to
increase. Granulocyte counts did not change, indicating that rolling is not
the main mechanism responsible for the marginal granulocyte pool.
Volume 77,
Issue 7,
pp. 1565-1571,
04/01/1991
Copyright © 1991 by The American Society of Hematology
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