Tuesday, January 24, 2012

Saturation of Phagocytic Capability of Macrophages by Clodrosome

Administration of high dose of particles such as saccharated iron oxide, thorotrast and polystyrene latex that can be ingested by macrophages may lead to saturation of the phagocytosis capability. In early studies on the role of phagocytosis in the induction of antibody responses, colloidal carbon particles or other finely divided compounds were studied. These particles however can not be degraded. by macrophages and will be ingested by new macrophages as soon as they are released from dying macrophages.

In the contrary, clodronate encapsulated liposomes (Clodrosome) are artificially prepared lipid spheres that have the same lipid composition as cells (unsaturated phosphatidylcholine and cholesterol) and can be degraded by macrophages. The natural fate of liposomes when administered in vivo is phagocytosis followed by intracellular degradation as a result of the action of lysosomal phospholipases.  Animation below shows the intracellular events that lead to apoptosis.



It has been shown that liposomal particles are also able to saturate the phagocytic activity of macrophages in a way that is similar to carbon particles. The first study about liposomal blockade of the reticuloendothelial was published in Nature in 1983:

http://www.sciencemag.org/content/220/4596/502.short

Contrary to the blocking of phagocytosis by particles such as carrageenan, dextran sulfate, gadolinium chloride and silica, liposomes do not stimulate the basic or lipoploysaccharide-induced production of pro-inflammatory cytokines and nitric oxide (NO) by macrophages and due to that the application of liposomes as a phagocytosis blocking agent offers the advantage of minimum side-effect on cytokine production and secretion.

For more information about macrophage depletion visit www.clodrosome.com 



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