title: A characteristic serpin cleavage product of thyroxine-binding globulin appears in sepsis sera.
abstract: 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.
authors.affiliation: Department of Medicine, State University of New York Health Sciences Center, Brooklyn 11203, USA.
authors.forename: B
authors.initials: B
authors.lastname: Jirasakuldech
authors.forename: G C
authors.initials: GC
authors.lastname: Schussler
authors.forename: M G
authors.initials: MG
authors.lastname: Yap
authors.forename: H
authors.initials: H
authors.lastname: Drew
authors.forename: A
authors.initials: A
authors.lastname: Josephson
authors.forename: J
authors.initials: J
authors.lastname: Michl
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008970:Molecular Weight; D009504:Neutrophils / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood / Q000302:isolation & purification; D018805:Sepsis / Q000097:blood*; D015843:Serpins / Q000097:blood*; D013974:Thyroxine / Q000378:metabolism; D013975:Thyroxine-Binding Proteins / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D015843:Serpins; D013975:Thyroxine-Binding Proteins; D010196:Pancreatic Elastase; D013974:Thyroxine