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

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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. / Garcia de Frutos, Pablo; Alim, R; Härdig, Ylva; Zöller, Bengt; Dahlbäck, Björn.

In: Blood, Vol. 84, No. 3, 1994, p. 815-822.

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Garcia de Frutos, Pablo; Alim, R; Härdig, Ylva; Zöller, Bengt; Dahlbäck, Björn / 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.

In: Blood, Vol. 84, No. 3, 1994, p. 815-822.

Research output: Contribution to journalArticle

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TY - JOUR

T1 - 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

AU - Garcia de Frutos,Pablo

AU - Alim,R

AU - Härdig,Ylva

AU - Zöller,Bengt

AU - Dahlbäck,Björn

PY - 1994

Y1 - 1994

N2 - 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.

AB - 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.

KW - Acute-Phase Proteins

KW - Acute-Phase Reaction

KW - Antibodies, Monoclonal

KW - Calcium

KW - Carrier Proteins

KW - Complement C4b

KW - Complement Inactivator Proteins

KW - Glycoproteins

KW - Humans

KW - Macromolecular Substances

KW - Protein S

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Article

VL - 84

SP - 815

EP - 822

JO - Blood

T2 - Blood

JF - Blood

SN - 1528-0020

IS - 3

ER -