Protein S enhances C4b binding protein interaction with neutrophils.
Protein S, an inhibitor of coagulation, interacts reversibly with C4b binding protein (C4bBP). The physiologic role of this complex formation remains unknown. In this study we examined the possibility that protein S would facilitate C4bBP binding to the surface of neutrophils where, in turn, this complex could help protect the cell from complement-mediated damage at the site of inflammation. Neutrophils bind approximately 60,000 protein S molecules per cell (kd = 140 nmol/L) in a Ca(2+)-dependent fashion. C4bBP also binds to neutrophils (23,000 sites per cell at physiologic C4bBP concentration), but this binding is not Ca2+ dependent. Protein S approximately doubled C4bBP binding, but protein S only influenced C4bBP binding in the presence of Ca2+. Protein S binding to neutrophils decreased approximately twofold in the presence of saturating concentrations of C4bBP. Neutrophil activation had only minor effects on the affinity and number of sites for protein S or the protein S-C4bBP complex. These results indicate that the protein S-C4bBP complex binds to the neutrophil surface where it can presumably modulate complement assembly on the cell surface.
Furmaniak-Kazmierczak
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Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
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Esmon
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D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D015935:Complement C4b / Q000378:metabolism*; D003169:Complement Inactivator Proteins; D004305:Dose-Response Relationship, Drug; D015943:Factor Va / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011486:Protein C / Q000494:pharmacology; D017293:Protein S / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism
D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D011486:Protein C; D017293:Protein S; D015943:Factor Va; D015935:Complement C4b; D013917:Thrombin; D016650:Fluorescein-5-isothiocyanate; D013755:Tetradecanoylphorbol Acetate