Lymphocytosis induced by polyanions in rats

More than twenty different polymers, mostly polyanions, were tested in rats for their ability to mobilize lymphocytes into the peripheral blood within 2--3 h. The various polyanions differed in basic structure, in side-chain (size and type), in molecular weight and configuration and in amount and type of anionic charge along the molecule. Neutral polymers and a polycation were also tested for comparison. Some of the polyanions were found to be very effective, others less so and some completely ineffective. Some were also toxic. The basic polymer to which the others were compared was polymethacrylic acid (PMAA), an already recognized mobilizing agent. The best agents were the heparinoids, sulphated polyanions, and the best of these, causing a 3--4-fold increase, were dextran sulphate and polyvinyl sulphuric acid (PVSA). Heparin, although the strongest anticoagulant, was the weakest mobilizer. Some factors that appear capable of modifying mobilization to varying degrees were molecular weight, size and configuration, sulphate content and mode of administration. In the case of PVSA, the smaller molecular weight substance gave a more prolonged lymphocytosis in blood. The high molecular weight substance gave a peak after 2 h, slightly earlier than with PMAA (2--3 h). The administration of protamine chloride to the rat (i.v.) caused an immediate reversal of mobilization, following a course to control values which was essentially identical to the normal decline, only earlier. Dextran sulphate of low molecular weight seems to be the polyanion of choice in subsequent mobilization experiments dealing with determination of the specific mononuclear cell type being mobilized. The single factor that all mobilizing polyanions have in common is a negative molecular charge. It is not yet known exactly how this charge induces the mobilization of mononuclear cells, nor what causes the variability in effectiveness among polyanions.