Abstract:

Recent studies have pointed out that highly cationic histones released by PMNs netosis may be major agents in autoimmune lupus since they have high affinity to various kidney sites and can be expected to play a key role in autoimmune glomerular disease.

Similarly to antibodies, cationic peptides such a nuclear histone can also act as potent opsonic agents capable of binding by strong electrostatic forces to negatively charged domains in immune complexes and in complement components resulting in their endocytosis and deposition in various parts of the kidney. It is also proposed that to prevent such events, highly anionic heparin and heparinoids, may be effective drugs since these may effectively neutralize histones activities but provided that agents such as steroids, methotrexate and colchicine, all potent inhibitors of neutrophils functions, and antibodies to TH1 cytokines be essential to treat nephritis and to prevent kidney failure. However, the main cause of kidney damage is eventually caused by the plethora of toxic pro inflammatory agents delivered by activated neutrophils and macrophages.

Publisher's Version