Silica carrageenan and dextran sulfate

30 years ago, administration of silica particles of defined dimensions was recommended as a procedure to deplete macrophages in vivo (3). The cytotoxicity of silica was found to be correlated with its capacity to disrupt the membranes of secondary lysosomes in macrophages, demonstrated by release of marker enzymes. More recent studies have shown that silica particles interact directly with both the plasma and lysosomal membranes. Results of the latter studies indicated that interaction of silica particles with the plasma membrane leads to Ca2+ influx with resultant cell death and ATP depletion, whereas their interaction with lysosomal membranes leads to release of lysosomal contents but is not followed by irreversible cell injury. That ATP depletion is involved in silica-mediated damage to macrophages has since been confirmed. Since the original description of the cytotoxic effects of silica on macrophages, macrophage depletion or blockade of phagocytosis by silica has been used in many studies aimed at the unravelling of macrophage functions in vivo.

However, like most other agents that are toxic for macrophages and block their phagocytic capability when administered in a high dose, sublethal doses of silica will stimulate cells of the monocyte/macrophage lineage to produce IL-1, IL-6, TNFa, and NO. Silica-induced production of cytokines by alveolar macrophages, especially TNFa, is a crucial factor in the induction of proliferation of fibroblasts in silicosis. As a consequence, silica-induced blocking of phagocytosis as a method to study macrophage function in vivo, can only be recommended if it can be excluded that one or more of the molecular products of macrophages play a regulatory role. This will be the case only rarely.

It has been reported that carrageenan, a sulfated polygalactose is cytotoxic to macrophages (4). Also other polyanionic polysaccharides such as dextran sulfate (DS 500) appeared to inhibit macrophage functions (5). Carrageenan and dextran sulfate have since been used for elimination or suppression of phagocytic activity or to reveal macrophage functions. However it has been confirmed that in addition to their effects on macrophages, carrageenan and dextran sulfate have a strong effect on lymphocytes. Moreover, both carrageenan and dextran sulfate enhanced the macrophage-mediated effects of LPS-induced septic shock and LPS-induced TNFa production. It was found that although treatment of macrophages with carrageenan reduced their phagocytic activity with respect to yeast cells, their ability to kill the yeast cells was increased. This may be explained by the increased production of molecules such as NO, which are thought to play a role in the killing of intraphagocytic micro-organisms. In conclusion, neither silica nor carrageenan or dextran sulfate can be recommended for blocking of macrophage functions.

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  • ottavia
    What has dextran sulfate in it?
    8 years ago

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