Tri-substituted organotin compounds, but not retinoic acid, are potent ligands of complement component 8 γ.

Complement component 8 gamma (C8 gamma) is a subunit of complement protein 8 (C8), which itself is a subunit of the complement cytolytic membrane attack complex. However, C8 gamma is also suggested to be a carrier protein for the general clearance of endogenous and exogenous compounds because it belongs to the lipocalin family of small secreted proteins that have the common ability to bind small hydrophobic ligands. Although retinoic acid, a metabolite of vitamin A, has been suggested as a potential ligand of C8 gamma, it remains unclear which other substances are able to bind to C8 gamma as ligands. Here, we evaluated the binding affinity of several organotin compounds that are ligands of a receptor of retinoic acid, retinoid X receptor, by using radioligand binding assays. The amount of [C-14]triphenyltin (TPT), a tri-substituted organotin, that bound to purified recombinant C8 gamma was increased with increasing protein concentration, whereas that of Mall-trans retinoic acid and [H-3]9-cis retinoic acid was unchanged. Scatchard analysis revealed that [C-14]TPT bound to C8 gamma with an equilibrium dissociation constant (K-d) of 56.2 +/- 16.2 nM. Non-radiolabeled tributyhin (TBT), another tri-substituted organotin, blocked the binding of [C-14]TPT to C8 gamma in a competitive manner, but non-radiolabeled mono- or di-substituted organotin compounds did not. Together, our present observations indicate that TBT and TPT, but not retinoic acid or mono- or di-substituted organotin compounds, are potent ligands of C8 gamma, suggesting that C8 gamma may be involved in the toxicities of these organotin compounds.