Why are clodronate liposomes useful for studying macrophage functioning?
Macrophages play an important role in the immune system. They regulate functions of many non-phagocytic cells, mainly through mediation of soluble molecules as cytokines and chemokines. Macrophages are also involved in ‘homoeostasis’ 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 hydrophilic molecules solved in aqueous solutions, such as clodronate, a non-toxic bisphosphonate developed for human application.
After injection, clodronate liposomes function as Trojan horses. Macrophages ingest the clodronate liposomes and digest the liposomal membranes. Clodronate is not digested and will remain inside the macrophage. More clodronate will accumulate in the macrophage as it ingests and digests more clodronate liposomes. At a certain intracellular concentration, clodronate will eliminate the macrophage by initiating its programmed cell death, i.e. apoptosis .
By choosing the right administration route of clodronate liposomes, particular organs or tissues can be depleted of macrophages. Therefore, clodronate liposomes are an excellent tool to study macrophage function .
1. Van Rooijen, N., & Hendrikx, E. (2010). Liposomes for specific depletion of macrophages from organs and tissues. In Liposomes (pp. 189-203). Humana Press.
2. Van Rooijen, N., Sanders, A., & van den Berg, T. K. (1996). Apoptosis of macrophages induced by liposome-mediated intracellular delivery of clodronate and propamidine. Journal of immunological methods, 193(1), 93-99.