Differential regulation of alpha and beta chains of C4b-binding protein during acute-phase response resulting in stable plasma levels of free anticoagulant protein S.
Regulation of C4b-binding protein (C4BP) isoforms during acute phase and its relationship to the plasma concentration of free protein S was elucidated. An assay for beta chain containing C4BP (C4BP beta+) was developed and the concentrations of total C4BP, C4BP beta+, total, free, and bound protein S were measured in patients with acute-phase response. Even though total C4BP was increased to 162% (mean value) of controls, the corresponding value of C4BP beta+ was only 122%. In the acute-phase group, total protein S was increased to the same extent as C4BP beta+ (mean value of 124%), whereas free protein S was not decreased. In controls, total and bound protein S correlated with total C4BP and C4BP beta+. However, in the acute-phase group, the correlation between bound protein S and total C4BP was lost, although the correlation between C4BP beta+ and protein S remained. The present results suggest stable levels of free protein S during acute phase to be the result of differential regulation of C4BP alpha- and beta-chain expression, and the concentration of free protein S to be the resulting molar excess of protein S over C4BP beta+. This mechanism ensures functional levels of free anticoagulant protein S despite high levels of C4BP.
García de Frutos
P
P
Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden.
Alim
R I
RI
Härdig
Y
Y
Zöller
B
B
Dahlbäck
B
B
D000209:Acute-Phase Proteins / Q000378:metabolism; D000210:Acute-Phase Reaction; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood* / Q000737:chemistry; D015935:Complement C4b / Q000378:metabolism; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D006801:Humans; D046911:Macromolecular Substances; D017293:Protein S / Q000097:blood*
D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D046911:Macromolecular Substances; D017293:Protein S; D015935:Complement C4b; D002118:Calcium