1991
DOI: 10.1152/ajpheart.1991.260.5.h1667
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Sulfated polysaccharides inhibit leukocyte rolling in rabbit mesentery venules

Abstract: 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 microns diam) of the rabbit mesentery. Leukocyte rolling was observ… Show more

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Cited by 70 publications
(71 citation statements)
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“…These results suggest that speciÂźc patterns of sulphation are involved in the e ects of heparin on mononuclear cell adhesion, or the relativeÂŻexibility of the heparin chain, which exists as an a-helix at physiological pH (Mulloy et al, 1996), possibly rendering sulphate charges more accessible to relevant binding sites on leucocytes, endothelial cells or inÂŻammatory mediators. Whereas dextran sulphates have been reported previously to inhibit neutrophil rolling in rabbit mesenteric venules (Ley et al, 1991), it is likely that such results, obtained in vivo, are a consequence of interference with carbohydrate interactions involved in leucocyte rolling, whereas our results reÂŻect a lack of e ect on Âźrm adhesion mechanisms relevant to mononuclear cells. Since O-desulphated heparin behaves in a similar way to unmodiÂźed heparin in our assays, it will be interesting to see the e ects of a selectively N-desulphated derivative of unfractionated heparin in such experiments, in order to investigate further the signiÂźcance of sulphate groups and their molecular location with respect to mononuclear cell adhesion.…”
Section: British Journal Of Pharmacology Vol 134 (4)contrasting
confidence: 66%
See 1 more Smart Citation
“…These results suggest that speciÂźc patterns of sulphation are involved in the e ects of heparin on mononuclear cell adhesion, or the relativeÂŻexibility of the heparin chain, which exists as an a-helix at physiological pH (Mulloy et al, 1996), possibly rendering sulphate charges more accessible to relevant binding sites on leucocytes, endothelial cells or inÂŻammatory mediators. Whereas dextran sulphates have been reported previously to inhibit neutrophil rolling in rabbit mesenteric venules (Ley et al, 1991), it is likely that such results, obtained in vivo, are a consequence of interference with carbohydrate interactions involved in leucocyte rolling, whereas our results reÂŻect a lack of e ect on Âźrm adhesion mechanisms relevant to mononuclear cells. Since O-desulphated heparin behaves in a similar way to unmodiÂźed heparin in our assays, it will be interesting to see the e ects of a selectively N-desulphated derivative of unfractionated heparin in such experiments, in order to investigate further the signiÂźcance of sulphate groups and their molecular location with respect to mononuclear cell adhesion.…”
Section: British Journal Of Pharmacology Vol 134 (4)contrasting
confidence: 66%
“…In addition, heparin is known to bind a number of adhesion molecules involved in leucocyte tra cking into tissues, including mac-1 (CD11b/CD18; Diamond et al, 1995) and L-selectin (Koenig et al, 1998) on inÂŻammatory cells and the endothelial adhesion molecules P-selectin (Revelle et al, 1996;Skinner et al, 1991) and platelet endothelial adhesion molecule-1 (PECAM-1; Watt et al, 1993). Accordingly, heparin and related molecules have been found to inhibit leucocyte-endothelial interactions both in vitro (Bazzoni et al, 1992;Lever et al, 2000;Silvestro et al, 1994) and in vivo (Ley et al, 1991;Salas et al, 2000;Xie et al, 1997), as well as inÂŻammatory cell accumulation in tissue sites such as the lung (Sasaki et al, 1993;Seeds et al, 1993), skin (Teixeira & Hellewell, 1993) and peritoneal cavity (Nelson et al, 1993). …”
Section: Introductionmentioning
confidence: 99%
“…Although the identity of the fucoidin-sensitive pathway remains unknown, it is conceivable that fucoidin, a heavily sulfated polysaccharide, may interfere with the ability of leukocytes to interact with sulfate-containing proteoglycans on the surface of vascular endothelium. Although this hypothesis is presently purely speculative, various other sulfated molecules have been shown to strongly interfere with leukocyte rolling in vivo (51)(52)(53) and leukocyte adhesion in vitro (54). Finally, the possibility exists that fucoidin is a more effective inhibitor of selectin function than the monoclonal antibodies, which may be only partially effective as blocking antibodies against feline selectins.…”
Section: Discussionmentioning
confidence: 99%
“…Before this stationary adhesion and the subsequent extravasation, the leukocytes roll along the venular endothelial lining at a much lower velocity than free-flowing blood cells ( 13,(17)(18)(19)(20)(21)(22). This dynamic and reversible type of leukocyte binding to the endothelium, not affected by anti-CD 18 mAbs ( 13,14), has recently been shown to be dependent on functional expression of leukocytic L-selectin ( 19,23,24), a carbohydrate-binding adhesion receptor belonging to the selectin family (25)(26)(27)(28).…”
Section: Introductionmentioning
confidence: 99%