title: Cleavage of thyroxine-binding globulin during cardiopulmonary bypass.
abstract: Thyroxine-binding globulin (TBG) is a noninhibitory member of the serine protease inhibitor (serpin) superfamily. A characteristic serpin cleavage product of TBG has been demonstrated in sera of septic patients. We find that a similar cleavage product appears in serum during the rapid decline of immunoassayable TBG and thyroxine (T(4)) that is associated with the inflammatory response to cardiopulmonary bypass (CPB). In vitro cleavage of TBG by the serine protease, neutrophil elastase induces a conformational change that has previously been shown to weaken affinity for T(4.) In vitro protease cleavage also decreases immunoassayable TBG, probably because the conformational change decreases the availability of the TBG epitopes to the measuring antibody. Thus, the rapid decrease in immunoassayable TBG concentration previously attributed to accelerated clearance is caused in part by the proteolytic cleavage per se. The evidence for proteolysis of TBG concurrent with the decrease in serum T(4) during CPB is consistent with the proposed release of T(4) from TBG to cells showing serine protease activity.
authors.affiliation: Division of Endocrinology, Department of Medicine, State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203-2098, 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: R
authors.initials: R
authors.lastname: Zirkind
authors.forename: B
authors.initials: B
authors.lastname: Afandi
authors.forename: J
authors.initials: J
authors.lastname: Michl
mesh_terms: D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D004591:Electrophoresis, Polyacrylamide Gel; D006358:Hot Temperature; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000097:blood* / Q000209:etiology; D019272:Leukocyte Elastase / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood; D012697:Serine Endopeptidases / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013974:Thyroxine / Q000097:blood; D013975:Thyroxine-Binding Proteins / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D012709:Serum Albumin; D013975:Thyroxine-Binding Proteins; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase; D013974:Thyroxine