The Role of Neutrophil Proteases in LPS-Induced Production of Regulatory Rheumatoid Factor that Suppresses Autoimmunity

Background: We recently identified a regulatory rheumatoid factor (regRF), the production of which is associated with autoimmune disease resistance and remission. In studies of regRF in the blood of healthy rats, spontaneous increases in the regRF level were noted. We suggest that in the normal state, a mechanism exists for maintaining the activity of the pool of regRF-producing lymphocytes at a level that makes it possible to control the expansion of autoreactive lymphocytes. Objective: The purpose of this study was to test the hypothesis that the endogenous stimulator of regRF production is Fc fragments of IgG that are formed upon exposure to the proteases of neutrophils. Results: Injection of Salmonella typhi LPS caused neutrophilic leukocytosis in the rats, followed by elevated level of regRF. Neutrophils were obtained from LPS-treated rats and then treated with LPS in vitro to degranulate them to form pre-split IgG that exposes antigenic determinants for regRF. A condition required for Fc fragments to be formed by neutrophils is that the pre-split IgG must be treated with a thiol reducing agent. Antigenic determinants for regRF were retained by Fc fragments of IgG. Conclusion: Thus, the pre-split IgG and Fc fragments of IgG formed by LPS-activated neutrophils are the potential physiological activators of regRF production.