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A Characteristic Serpin Cleavage Product of Thyroxine-Binding Globulin Appears in Sepsis Sera

Division of Endocrinology, Department of Medicine (B.J., G.C.S., M.G.Y.); Division of Immunology, Department of Medicine (H.D., A.J.); and Departments of Pathology, Anatomy, and Cell Biology and Microbiology and Immunology (J.M.), State University of New York Health Sciences Center, Brooklyn, New York 11203

Address all correspondence and requests for reprints to: Dr. George C. Schussler, Division of Endocrinology, Department of Medicine, State University of New York Health Sciences Center, Brooklyn, New York 11203. E-mail: george.c.schussler-new-york{at}worldnet.att.net

T₄-binding globulin (TBG), the principal thyroid hormone-binding protein of serum, is a member of the serine protease inhibitor (serpin) superfamily. We report a characteristic serpin cleavage product of TBG in sepsis sera. At 49–50 kDa, the TBG remnant is 4–5 kDa smaller than the intact protein and is the same molecular mass as a TBG cleavage product produced by incubation with polymorphonuclear elastase. Incubation with polymorphonuclear leukocytes also produces the 49- to 50-kDa remnant, and this proteolysis is stimulated by zymosan activation. Polymorphonuclear cell cleavage of TBG increases the ratio of free/bound T₄. As previously described, in vitro cleavage of TBG by elastase also increases free/bound T₄. These findings are consistent with the hypothesis that serine proteases present at inflammatory sites cleave TBG, releasing its hormonal ligands.

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