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Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling
in venules of the rat mesentery
K Ley, G Linnemann, M Meinen, LM Stoolman and P Gaehtgens
Department of Physiology, Freie Universitat Berlin, Germany.
Leukocyte rolling in venules is inhibited by several sulfated
polysaccharides, by antibodies to the leukocyte adhesion receptor L-
selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated
fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin
and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high
endothelial venules (LN-HEV). We investigated whether fucoidin and PPME
also inhibit leukocyte rolling. Rolling leukocyte flux was determined by
intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat
mesentery with and without micro-infusion of each reagent through 8-microns
glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection
(25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by
greater than 90%. The half- effective concentration was approximately 2.5
micrograms/mL. Stroboscopic fluorescence video microscopy showed that
fucoidin decreased the fraction of rolling leukocytes from 44% of all
leukocytes passing the venules in control to less than 1%. PPME
micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce
leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing
with respect to the effect of PPME. This may be related to fucoidin binding
to L- selectin with greater affinity than PPME. Alternatively, inflamed
venular endothelium may express a ligand for L-selectin different from that
constitutively expressed on LN-HEV.
Volume 81,
Issue 1,
pp. 177-185,
01/01/1993
Copyright © 1993 by The American Society of Hematology
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