Immune cell membranes and lysosomal compartments

Immune cell membranes and lysosomal compartments refer to the structural organelles and lipid bilayers within leukocytes that facilitate essential immune processes such as antigen presentation and signal transduction (Schrezenmeier & Dörner, 2020). These compartments are characterized by an acidic internal environment maintained by V-ATPase proton pumps, which is crucial for the activity of various hydrolases and the maturation of endosomes (Ohkuma & Poole, 1978). In the context of pharmacology, these structures are the primary site of accumulation for lysosomotropic drugs like hydroxychloroquine, which partition into the membranes and concentrate within the lysosomal lumen (Kuznik et al., 2011). This accumulation raises the intra-lysosomal pH, thereby inhibiting the proteolytic processing of autoantigens and the activation of endosomal Toll-like receptors (TLRs) such as TLR7 and TLR9 (Wallace et al., 2012). Consequently, the disruption of these compartments modulates the inflammatory response in autoimmune diseases like systemic lupus erythematosus and rheumatoid arthritis (Mauthe et al., 2018). However, because this term describes a collection of cellular structures rather than a specific protein or enzyme, it is classified as a cellular location rather than a discrete molecular target.

Other names

Endolysosomal systemLysosomal compartmentAcidic vesiclesLeukocyte membranes

Lysosomotropic accumulation within acidic compartments leads to an increase in intralysosomal pH, which inhibits acid-dependent hydrolases (such as cathepsins) and interferes with the processing and signaling of endosomal Toll-like receptors (TLR7 and TLR9) (Schrezenmeier & Dörner, 2020; Kuznik et al., 2011).