title: The soluble recombinant form of a binding protein/receptor for the globular domain of C1q (gC1qR) enhances blood coagulation.
abstract: The gC1qR is a ubiquitously expressed, 33 kDa cellular protein which recognizes the globular domains of C1q. Recent evidence suggests that the gC1qR also serves as the Zn(++)-dependent endothelial cell binding site for factor XII and high-molecular-weight kininogen, and activates intrinsic coagulation and kinin pathways in purified systems. In addition, activated lymphocytes have been reported to release soluble gC1qR. Thus, the present study investigated the procoagulant potential of soluble gC1qR in human plasma using the recombinant protein (rgC1qR). rgC1qR supported a dose-dependent shortening of extrinsic coagulation using the prothrombin time in the presence of diluted (1/50-1/500) thromboplastin. Maximum enhancement of the prothrombin time resulted in shortening of the clotting time from 78.8 +/- 0.4 s to 68.5 +/- 0.6 s (mean +/- SD, n = 8) in the presence of 50 micrograms/ml (1.5 mumol/l) rgC1qR. rgC1qR also enhanced the intrinsic pathway of coagulation evaluated in the absence of activators of the contact system, as demonstrated by a shortening of the plasma recalcification time from 348 +/- 66 s to 140 +/- 23 s (n = 4). rgC1qR, however, had no effect on intrinsic coagulation in the presence of undiluted kaolin or ellagic acid, and under these conditions failed to shorten the activated partial thromboplastin time of factor VIII or factor-IX-deficient plasma. rgC1qR further failed to affect thrombin and factor Xa generation assayed using chromogenic substrates, and did not enhance thrombin-induced conversion of fibrinogen to fibrin. Interestingly, the procoagulant activity of the rgC1qR was measurable in either factor-XII- or factor-XI-deficient plasma, suggesting that it was not exclusively focused on the contact system of coagulation. Although the mechanism of action of gC1qR on blood coagulation remains obscure, the data suggest a potential role for this protein in hemostatic and thrombotic events.
authors.affiliation: New York Hospital-Cornell Medical College, New York 10021, USA. epeersch@mail.med.cornell.edu
authors.forename: E I
authors.initials: EI
authors.lastname: Peerschke
authors.forename: J
authors.initials: J
authors.lastname: Jesty
authors.forename: K B
authors.initials: KB
authors.lastname: Reid
authors.forename: B
authors.initials: B
authors.lastname: Ghebrehiwet
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects* / Q000235:genetics; D001780:Blood Coagulation Tests; D002352:Carrier Proteins; D015922:Complement C1q / Q000378:metabolism*; D005173:Factor XI Deficiency / Q000097:blood; D005175:Factor XII Deficiency / Q000097:blood; D015951:Factor Xa / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011485:Protein Binding; D011951:Receptors, Complement / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology*; D012995:Solubility; D013917:Thrombin / Q000378:metabolism
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D011994:Recombinant Proteins; C032402:complement 1q receptor; D015922:Complement C1q; D013917:Thrombin; D015951:Factor Xa