Effects of dextran sulphate and heparin on lymphocyte localization: Lack of involvement of complement and other plasma proteolytic systems

The effects of subcutaneously administered dextran sulphate (50 mg/kg) and heparin (200 i.u.) on the subsequent 1–3 h localization of intravenously injected radiolabelled lymph node cells was investigated. Radioactivity was reduced in lymph nodes, Peyer's patches and small intestine and increased in blood, lungs and (often) spleen. Systemic effects of a single dose of dextran sulphate (DXS) disappeared within three days, but the regional lymph nodes still showed subnormal localization after five days. Prior local injection of sheep erythrocytes modified the response to dextran sulphate locally, and to heparin both locally and systemically. The smallest doses to show any detectable effect were 5 mg/kg of dextran sulphate and 2 i.u. of heparin. Mice rapidly become refractory to the effects of dextran sulphate; this was not attributable to formation of anti-dextran antibodies. Despite its inhibitory effects on the localization of lymphocytes from blood into lymph nodes, dextran sulphate treatment led to increases in cellularity and proliferative activity in regional lymph nodes within five to seven days and had a modest adjuvant effect on the antibody response to sheep erythrocytes. Cobra venom factor, aprotinin, ε-amino caproic acid and bradykinin all failed to influence lymphocyte localization or modify the effects of dextran sulphate. The mechanism whereby sulphated polyanions act on lymphocyte localization remains unclear. The development of refractoriness to dextran sulphate suggests that this substance does not simply interfere directly with the interaction between lymphocytes and endothelial cells of the post-capillary venules. On the other hand, there was no evidence to suggest that dextran sulphate or heparin act through the intermediacy of complement or other plasma proteolytic systems, despite their well-known ability to interact with these systems in vitro.