Polyreactive Transformation of Class G Immunoglobulins as a Vector for Search of Potential Means for Improving the Activity of Anti-endotoxin Immunity

Abstract

Short-term in vitro exposure of a chaotropic reagent to native class G immunoglobulins can significantly increase the activity of anti-endotoxin immunity and cause a decrease in the ability of effector cells for enterobacteria lipopolysaccharides (LPS). This leads to reducing the LPS-dependent activation of these cells and subsequent inflammation. This can be useful not only for the treatment of septic patients, but also for the prevention of the progression of diseases of atherosclerotic nature, because LPS is considered to be the most important factor in the induction of atherogenesis. The polyreactive transformation mechanism of native class G immunoglobulins under the influence of a chaotropic reagent remains unknown. It can consist in the induction of intramolecular conformational rearrangements of native γ-globulins. As a result, “ancestral” sites of low-affinity multispecific binding appear on Fab fragments, which determines the appearance of complementarity to evolutionarily stable molecular structures of pathogens. The results indicate the need for further investigation of the polyreactive transformation mechanisms of native class G immunoglobulins and the search for nontoxic chaotropic agents that could potentially be used in clinical practice.