The effect of the selectin binding polysaccharide fucoidin on eosinophil recruitment in vivo

Abstract

In order to accumulate at sites of inflammation, leukocytes initially roll on endothelial cells of post‐capillary venules before becoming firmly attached. This process of rolling is mediated by selectins which bind to carbohydrate counter‐ligands present on the surface of both leukocytes and endothelial cells. The polysaccharide fucoidin has been previously shown to inhibit leukocyte rolling in the mesenteric circulation and to reduce neutrophil accumulation in the skin and meninges in experimental inflammation. In the present study we have assessed the effects of fucoidin on eosinophil function in vitro and eosinophil accumulation at sites of inflammation in guinea‐pig skin. At concentrations of up to 1200 μg ml−1, fucoidin inhibited phorbol myristate acetate (PMA)‐induced eosinophil homotypic aggregation by up to 60% but had no inhibitory effect on PMA‐induced eosinophil adhesion to serum‐coated plates. Fucoidin effectively reduced the binding of the anti‐L‐selectin mAb MEL‐14 to guinea‐pig eosinophils. Binding of a P‐selectin‐IgG chimera to eosinophils was also partially inhibited by fucoidin, but binding of an anti‐CD18 or an anti‐VLA‐4 mAb were unaffected. When given systemically to guinea‐pigs, fucoidin suppressed 111In‐labelled eosinophil recruitment to sites of allergic inflammation. 111In‐labelled eosinophil accumulation induced by platelet‐activating factor (PAF) and zymosan‐activated plasma (as a source of C5a des Arg) was also inhibited. These results demonstrate a role for fucoidin‐sensitive selectins in mediating eosinophil recruitment in vivo. British Journal of Pharmacology (1997) 120, 1059–1066; doi:

Selectins and integrins but not platelet–endothelial cell adhesion molecule‐1 regulate opioid inhibition of inflammatory pain

“…Fucoidin produced either no change (granulocytes and monocytes/ macrophages) or a drop (T cells) in the number of circulating leukocytes. This was also observed by others (Kuebler et al, 1997;Teixeira & Hellewell, 1997) and has been related to anaphylactoid reactions to sulfated polysaccharides such as fucoidin (Kuebler et al, 1997). Notwithstanding, our functional together with morphological findings indicate that L-and P-selectins and the integrins a 4 and b 2 permit the , and PECAM-1 on stress-induced antinociception.…”

“…The number of T cells was reduced by fucoidin but not by anti-a 4 combined with anti-b 2 , which could be due to lower baseline counts of T cells in anti-integrin-compared with fucoidin-treated groups (Figure 4a and c). Blockade of leukocyte extravasation can result in no change or elevated cell numbers in the blood (Teixeira & Hellewell, 1997;. Consistently, combined treatment with anti-a 4 and anti-b 2 increased circulating leukocyte counts.…”

Intracisternally Localized Bacterial DNA Containing CpG Motifs Induces Meningitis

“…This is the first and essential step in the process of leukocyte extravasation into inflamed sites (31,36). In bacterial meningitis, treatment with L-and P-selectin-binding fucoidin (37,38) has been shown to attenuate meningeal inflammation, abolish pleocytosis, and inhibit the release of TNF-␣ and IL-1 in a rabbit model of meningitis induced by pneumococcal cell wall fragments (19,59). The fact that fucoidin did not completely abrogate meningitis induced by CpG ODN indicates that E-selectin might also be required for development of the meningitis.…”

“…To understand this process, we analyzed the role of selectins since these molecules mediate leukocyte rolling, and thus control early steps of extravasation of leukocytes during inflammation (36). To this end, we used fucoidin, which has the ability to block P-and L-selectins (19,37,38). Mice were treated with fucoidin either i.v.…”

Cosmeceuticals Derived from Bioactive Substances Found in Marine Algae

“…When compared to its mammalian analogue, heparin, fucoidan has greater potential for use as a topical anti-inflammatory for cosmetic after sun products, allergic skin condition soothing products or specialty postsurgical products, to inhibit eosinophilia due to its greater stability [63].…”