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Recent column (July 06, 2015): Onze gezamenlijke voorouders binnen de orde der gewervelde dieren
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- Please note: A new website <www.clodronateliposomes.com> is available for ordering of clodronate liposomes and control liposomes containing no clodronate. Please click on ORDER LIPOSOMES in the above MENU of the present site, to go directly to the order page of the new site.
- The new website will also show you a list of current projects brought up to date. The present website will show the list of publications brought up to date.
- Since 1. NvR is no longer involved in active research and will not be aware of all newly published research on macrophage function for that reason , and 2. Research using clodronate liposomes to study and/or manipulate macrophage function will be continuously extended, there will be many scientists having information that could be of much help to other scientists in macrophage research, but can nevertheless not be found when visiting this website. So, I would suggest that scientists who do have newly published information on the use of clodronate liposomes for studies on the role of phagocytic cells or their manipulation, would let me know about this. In particular, depletion of specific monocyte subsets and the relevant administration routes of the clodronate liposomes could be of interest, provided that full information regarding the experimental procedures, has been published. Full reference to their published results should be added so that this may help other scientists. As soon as questions on this point will reach me <nvanrooijen@ClodronateLiposomes.org>, I will certainly prepare a relevant FAQ section in the INFORMATION section of the present website, in which the relevant reference will be given in full. In turn this will rapidly bring your published findings under the attention of those who are eagerly waiting to read it. Regards, Nico van Rooijen
Liposomes as a tool to manipulate macrophage function
From an evolutionary point of view, macrophages are ancient cells. They form the core of the natural immune system and did appear long before the cells forming together the complex immune system of the higher vertebrates. As a consequence, during the evolution, they did acquire functions both in natural immune reactions and in the regulation of functions of many non-phagocytic cells. The latter functions are mainly mediated by soluble molecules such as cytokines and chemokines.
Macrophages are also involved in 'homoiostasis' of the body by ingesting and digesting microorganisms or non-self particles and macromolecules. Digestion is in turn mediated by their lysosomal enzymes.
Liposomes are artificially prepared lipid vesicles, consisting of concentric phospholipid bilayers entrapping aqueous compartments. They can be used to encapsulate strongly hydropihilic molecules solved in aqueous solutions, such as clodronate, a non-toxic bisphosphonate, developed for human application. Freely solved clodronate will not cross liposomal or cellular phospholipid membranes. After injection, liposomes, used as Trojan horses in this case, will be ingested and digested by macrophages followed by intracellular release and accumulation of clodronate. At a certain intracellular concentration, clodronate induces apoptosis of the macrophage. By this approach, i.e. by creating an animal with macrophage depleted tissues or organs, functional aspects of macrophages are studied 'in vivo' in many collaborative projects.
Moreover, promising results were obtained by application of clodronate liposomes for suppression of macrophage activity in various models of autoimmune diseases, transplantation, neurological disorders and gene therapy.