An HMG-I protein from human endothelial cells apparently is secreted and impairs activation of Hageman factor (factor XII).
A highly purified protein from lysates of human umbilical vein endothelial cells (HUVECs) inhibited the activation of factor XII [Hageman factor (HF)] and removed factor XIIa from an activating surface, thus impairing HF-dependent coagulation and kinin-releasing activities. Two tryptic peptides from this protein had 100% identity with amino acids 31-44 and 89-101 of a nonhistone DNA-binding protein known as high-mobility group protein (HMG-I). In specific antibody experiments, the clot-inhibiting property in purified lysate protein from HUVECs was associated with HMG-I. The molecular weight of the protein that inhibited clotting was consistent with that predicted for HMG-I. Protein that inhibited contact activation and had antigenic properties of HMG-I and HUVEC lysate protein also was found in conditioned media from unchallenged cultured HUVECs. After HUVECs were incubated with 14C lysine, conditioned media contained immunoprecipitable radiolabeled protein with the same molecular weight as that recovered from cell lysates, suggesting that this high-mobility group protein (HMG-I) may be secreted. Purified factor XII antigens were displaced from a glass surface by HMG-I from lysates in proportion to the amount of HMG-I protein that was added. This HMG-I probably inhibits factor XII functions because its high positive charge favors competitive binding to an activating substance.
Donaldson
V H
VH
Department of Pediatrics, University of Cincinnati College of Medicine, OH, USA.
Wagner
C J
CJ
Mitchell
B H
BH
Mandle
R
R
D000595:Amino Acid Sequence; D001777:Blood Coagulation; D002478:Cells, Cultured; D003029:Coagulants / Q000494:pharmacology; D004610:Ellagic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005174:Factor XII / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007705:Kinins / Q000378:metabolism; D008969:Molecular Sequence Data
D003029:Coagulants; D006609:High Mobility Group Proteins; D007705:Kinins; D004610:Ellagic Acid; D005174:Factor XII