Structural changes of plasma high molecular weight kininogen after in vitro activation and in sepsis.
High molecular weight kininogen (HMWK) is a multifunctional protein that is a parent molecule for bradykinin, a cofactor for coagulation, and an inhibitor of cysteine proteases. On immunoblot, nonreduced plasma HMWK is usually two bands at 140 kd and 120 kd; reduced plasma HMWK is a single band at 120 kd. In both concentration-dependent and time-dependent experiments kaolin-activated normal plasma HMWK becomes cleaved in an ordered sequence. When nonreduced, HMWK on immunoblot in kaolin-activated plasma changes in size from a 140 kd band through a 120 kd intermediate to result in a stable 100 kd protein. When reduced, HMWK on immunoblot in kaolin-activated plasma changes from a single 120 kd band through a 56 kd intermediate to result in a stable 46 kd protein. A similar sequence of cleavage of plasma HMWK occurs when the soluble activator dextran sulfate is used to stimulate the system. Cleavage of plasma HMWK after kaolin activation occurs similarly in factor XI-deficient plasma as in normal plasma but is decreased in prekallikrein-deficient plasma. Prolonged kaolin activation of prekallikrein-deficient plasma results in HMWK cleavage to bands below 120 kd. No band of plasma HMWK below 120 kd appears in prolonged kaolin-activated factor XII-deficient plasma. In some patients with sepsis, detectable cleavage of plasma HMWK to bands below 120 kd may not be seen, even though the patient has other evidence for contact system activation. In conclusion, these studies indicate that certain cleaved patterns of plasma HMWK on immunoblot indicate prior activation of the contact system. However, the absence of these cleaved forms of plasma HMWK in a single plasma does not exclude the occurrence of contact activation.
Schmaier
A H
AH
Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140.
Farber
A
A
Schein
R
R
Sprung
C
C
D001424:Bacterial Infections / Q000097:blood*; D001779:Blood Coagulation Factors / Q000502:physiology; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology; D006801:Humans; D007118:Immunoassay; D007616:Kaolin / Q000494:pharmacology; D007704:Kininogens / Q000032:analysis / Q000097:blood*; D008934:Mitogens / Q000494:pharmacology
D001779:Blood Coagulation Factors; D003911:Dextrans; D007704:Kininogens; D008934:Mitogens; D007616:Kaolin; D016264:Dextran Sulfate