1. In order to accumulate at sites of
inflammation, leukocytes initially roll on endothelial cells of postcapillary 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. 2. 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. 3. At concentrations of up to 1200 micrograms 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. 4.
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. 5. 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. 6. These results demonstrate a role for
fucoidin-sensitive
selectins in mediating eosinophil recruitment in vivo.