IgG immunoglobulins induce activation of the sphingomyelin cycle in HL-60 cells

AbstractIn HL-60 cells signal transduction via sphingomyelin hydrolysis (sphingomyelin cycle) is induced by binding of tumor necrosis factor α (TNFα) to cell surface TNFα receptor. We found that IgG immunoglobulins activate sphingomyelin hydrolysis in plasma membrane of HL-60 cells, with kinetics similar to that of activation by TNFα. Activation was induced by different IgG isotypes (most of which are irrelevant to known inducers of the sphingomyelin cycle) and also by Fcγ fragments of IgG. The facts that inhibiting the binding of the antibodies to the cell surface by protein A prevents activation of sphingomyelin hydrolysis and that soluble TNF receptor of 55-kDa subtype (TBP55) inhibits activation, suggest that the mechanism of IgG-induced sphingomyelin hydrolysis involves binding of IgGs through their Fcγ domain to Fcγ surface receptors which mediate autocrine secretion of TNFα. The latter is responsible for inducing sphingomyelin hydrolysis. This study suggests that TBP55 may be an effective inhibitor of the sphingomyelin cycle