Protein S and C4b-binding protein levels in patients with stroke: implications for protein S regulation.
Protein S circulates either free or bound to C4b-binding protein (C4b-BP). Only free protein S possesses cofactor activity for protein C, a physiologic anticoagulant. Deficiencies of either protein C or protein S are associated with increased thrombotic risk. Over a 23-month period, 40 patients with low free protein S were identified. Eight of these patients were found to have suffered a stroke. This study examined the relationship between total S, free S, and C4b-BP in 15 healthy adult volunteers, in 20 patients with normal protein S levels, in 40 patients with decreased free protein S levels, and in 8 patients with combined low free S levels and stroke. Total and free protein S and C4b-BP levels were determined using the method of Laurell. In healthy adults, free protein S increased with increasing total protein S (r = 0.60). In patients with normal free S, the total S level increased as C4b-BP increased (r = 0.74), and the free S level remained constant. In patients with low free S, total S did not increase with increasing C4b-BP. In stroke patients, the correlation between free S and total S was actually negative (r = -0.449). Evaluation of dissociation constants for the protein S-C4b-BP complex revealed enhanced binding in patients with low levels of free protein S. A non-C4b-BP protein S binding protein, a previously undescribed regulatory factor which modulates S binding to C4b-BP, or shifts in the amount of non-protein S binding C4b-BP are possible explanations of these results.
Carr
M E
ME
Department of Medicine, Medical College of Virginia, Richmond.
Zekert
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SL
D000328:Adult; D002352:Carrier Proteins / Q000097:blood*; D002561:Cerebrovascular Disorders / Q000097:blood*; D015935:Complement C4b / Q000378:metabolism*; D003169:Complement Inactivator Proteins; D005260:Female; D006023:Glycoproteins; D006801:Humans; D008297:Male; D017293:Protein S / Q000097:blood*; D011951:Receptors, Complement / Q000378:metabolism*
D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D017293:Protein S; D011951:Receptors, Complement; D015935:Complement C4b