Hydrogen sulfide (H2S) has emerged as an important biological mediator with numerous pathophysiological roles. One of the well-documented actions of H2S is to inhibit immunity, especially cellular immunity. Currently, limited information is available regarding its effects on humoral immunity. Given that H2S has reducing activity and that the effector molecules in humoral immunity, such as antibody and complement, contain abundant disulfide bonds that are indispensable for their functions, we speculated that H2S might regulate antibody activity via modification of disulfide bonds. Here we addressed this possibility. Exposure of antibodies to H2S donors resulted in cleavage of the disulfide bonds between the heavy and light chains of antibodies, which was associated with antibody sulfhydration. Further analysis revealed that H2S-treated antibodies exhibited a marked reduction in antigen binding ability. It potently prevented the antibody-mediated agglutination of red blood cells and interrupted aggregation of antibody-coated microspheres. H2S also greatly inhibited antibody-induced and complement-mediated cell lysis in glomerular mesangial cells, as well as anti-CD95 IgM antibody-initiated cell apoptosis in Jurkat cells. Moreover, it significantly suppressed the alternative complement activation pathway. Collectively, our results revealed, for the first time, that pharmacologic levels of H2S inhibit humoral immune responses via direct sulfhydration of the effector molecules. Our study thus provides novel mechanistic insights into the immunoregulatory actions of H2S and suggests that H2S may have potential to treat certain humoral immune diseases.
Keywords: Antibody; Apoptosis; Complement; Hydrogen sulfide; Jurkat cells; Sulfhydration.
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