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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

Keyword

Acute-Phase Proteins

Acute-Phase Reaction

Antibodies, Monoclonal

Calcium

Carrier Proteins

Complement C4b

Complement Inactivator Proteins

Glycoproteins

Humans

Macromolecular Substances

Protein S

Journal Article

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

Publication and Content Type

art (subject category)

ref (subject category)