scholarly journals An essential role of high-molecular-weight kininogen in endotoxemia

2017 ◽  
Vol 214 (9) ◽  
pp. 2649-2670 ◽  
Author(s):  
Aizhen Yang ◽  
Zhanli Xie ◽  
Bo Wang ◽  
Robert W. Colman ◽  
Jihong Dai ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Light Chain ◽  
Essential Role ◽  
High Molecular Weight Kininogen ◽  
Core Oligosaccharide ◽  
E Coli ◽  
Chain Form ◽  
Deficient Mice

In this study, we show that mice lacking high-molecular-weight kininogen (HK) were resistant to lipopolysaccharide (LPS)-induced mortality and had significantly reduced circulating LPS levels. Replenishment of HK-deficient mice with human HK recovered the LPS levels and rendered the mice susceptible to LPS-induced mortality. Binding of HK to LPS occurred through the O-polysaccharide/core oligosaccharide, consistent with the ability to bind LPS from K. pneumoniae, P. aeruginosa, S. minnesota, and different E. coli strains. Binding of LPS induced plasma HK cleavage to the two-chain form (HKa, containing a heavy chain [HC] and a light chain [LC]) and bradykinin. Both HKa and the LC, but not the HC, could disaggregate LPS. The light chain bound LPS with high affinity (Kd = 1.52 × 10−9 M) through a binding site in domain 5 (DHG15). A monoclonal antibody against D5 significantly reduced LPS-induced mortality and circulating LPS levels in wild-type mice. Thus, HK, as a major LPS carrier in circulation, plays an essential role in endotoxemia.

scholarly journals Significant Role of Fragment 1·2 Plus Light Chain of Bovine High Molecular Weight Kininogen in Contact Mediated Coagulation

1977 ◽  
Author(s):  
R. Waldmann ◽  
A. G. Scicli ◽  
G. M. Scicli ◽  
J. A. Guimaraes ◽  
O. A. Carretero ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Light Chain ◽  
Active Site ◽  
Urinary Kallikrein ◽  
High Molecular Weight Kininogen ◽  
Molar Basis ◽  
Hydrolysis Of ◽  
Effect Of Light

We have previously reported that high molecular weight kininogen (HMWK) partially corrects the partial thromboplastin time (aPTT) of Fitzgerald Trait plasma (HMWK deficiency), and in addition, we have also reported that kinin free HMWK which is also Fragment 1·2 free has decreased correcting capability. Presently, we have studied the effect of lysyl-bradykinin-free HMWK with Fragment 1·2 intact, obtained by hydrolysis of HMWK with urinary kallikrein. In addition, the effect of light chain with and without attached Fragment 1·2 were studied. When the correcting capacity of HMWK was compared, on a molar basis with the above-mentioned fragments, the following results were obtained. Kinin and Fragment 1.2 free HMWK has a significantly decreased correcting capacity on the aPTT of Fitzgerald trait plasma while lysyl-bradykinin free HMWK shows no decrease in correcting capability. Light chain with Fragment 1·2 attached also has intact correcting capability while light chain alone has a significantly decreased correcting activity. The above data suggest that the active site of HMWK resides in the light chain with Fragment 1·2 attached. Since Fragment 1·2 alone has inhibitory capacity, it may serve as a binding site and the light chain as the active site.

scholarly journals Correction: An essential role of high-molecular-weight kininogen in endotoxemia

2018 ◽  
Vol 216 (1) ◽  
pp. 244-244
Author(s):  
Aizhen Yang ◽  
Zhanli Xie ◽  
Bo Wang ◽  
Robert W. Colman ◽  
Jihong Dai ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Essential Role ◽  
High Molecular Weight Kininogen

scholarly journals The Role of High Molecular Weight Kininogen and Prothrombin as Cofactors in the Binding of Factor XI A3 Domain to the Platelet Surface

2000 ◽  
Vol 275 (33) ◽  
pp. 25139-25145 ◽  
Author(s):  
David H. Ho ◽  
Karen Badellino ◽  
Frank A. Baglia ◽  
Mao-Fu Sun ◽  
Ming-Ming Zhao ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
High Molecular Weight Kininogen ◽  
Factor Xi ◽  
Platelet Surface

Commercial Immunodepleted Deficient Plasmas Contain Cleaved High Molecular Weight Kininogen (HK)

1988 ◽  
Vol 60 (03) ◽  
pp. 447-452
Author(s):  
C Mannhalter ◽  
H Lang
Keyword(s):  
Molecular Weight ◽  
Quality Control ◽  
Comparative Analysis ◽  
High Molecular Weight ◽  
Control Method ◽  
Immunoblot Analysis ◽  
High Molecular Weight Kininogen ◽  
Single Chain ◽  
Quality Control Method ◽  
Chain Form

SummaryComparative analysis of high molecular weight kininogen (HK) in various commercial congenital and immunodepleted deficiency plasmas was performed by immunoblotting of HK. It was found, that some artificially depleted deficiency plasmas contained proteolytically cleaved, kinin-free kininogen. In contrast, in all congenitally deficient plasmas, HK was present in the intact, single chain form. Thus, cleavage of kininogen could have been triggered by or during the immunodepletion procedure. It was seen, that the degree of proteolytic cleavage and degradation of HK in depleted plasmas differed among various manufacturers. E.g. depleted products of one company contained only trace amounts of cleaved HK, in contrast to products of another one, in which HK was completely degraded. The immunoblot analysis of HK reflects the occurrence of proteolytic events during the production of artificially deficient plasmas and can therefore serve as a quality control method.

Corrections - High Molecular Weight Kininogen or its Light Chain Protects Human Plasma Kallikrein from Inactivation by Plasma Protease Inhibitors

Biochemistry ◽  
1982 ◽  
Vol 21 (12) ◽  
pp. 3036-3036
Author(s):  
Marc Schapira ◽  
Cheryl Scott ◽  
Ann James ◽  
Lee Silver ◽  
Frederich Kueppers ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Human Plasma ◽  
High Molecular Weight ◽  
Protease Inhibitors ◽  
Light Chain ◽  
Plasma Kallikrein ◽  
High Molecular Weight Kininogen
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