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

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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:10.1038/sj.bjp.0701024