Role of the Light Chain of High Molecular Weight Kininogen in Adhesion, Cell-Associated Proteolysis and Angiogenesis

2001 ◽  
Vol 382 (1) ◽  
Author(s):  
Robert W. Colman
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Light Chain ◽  
High Molecular Weight Kininogen

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 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

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

scholarly journals Relationship between structure and correcting activity of bovine high molecular weight kininogen upon the clotting time of fitzgerald-trait plasma

1979 ◽  
Vol 149 (4) ◽  
pp. 847-855 ◽  
Author(s):  
AG Scicli ◽  
R Waldmann ◽  
JA Guimaraes ◽  
G Scicli ◽  
OA Carretero ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Heavy Chain ◽  
Light Chain ◽  
Plasma Kallikrein ◽  
High Molecular Weight Kininogen ◽  
Clotting Time ◽  
Active Inhibitor ◽  
Charged Surfaces ◽  
Bovine Plasma

Bovine high molecular weight kininogen (bHMWK) partially corrects the activated plasma thromboplastin time (aPTT) of Fitzgerald trait plasma which is congenitally deficient in HMWK. The relationship between the structure and activity of HMWK was clarified by studying the effects of different fragments of bHMWK on the aPTT of Fitzgerald-trait plasma. The peptides studied were lys-bradykinin-free HMWK, bradykinin-fragment 1-2-free HMWK, heavy chain, fragment 1-2-light chain, and light chain. All fragments were tested in equimolar concentrations. Bradykinin-fragment 1-2-free HMWK, heavy chain, and light chain have little or no correcting activity upon Fitzgerald-trait plasma aPTr. Fragment 1-2 light chain has the same correcting activity as intact bHMWK, while that of lys-bradykinin-free HMWK appears to be higher. Both fragment 1-2 and fragment 2 inhibit the clotting time of normal human plasma. When compared on a molar basis, fragment 2 is a more active inhibitor than fragment 1-2. When the effects of bovine plasma kallikrein upon bHMWK and hHMWK were studied, it was found that it released kinins from both kininogens. However, while the correcting activity of bHMWK was completely destroyed after 60 min of incubation, that of hHMWK was fully retained. These data suggest that: (a) the active part of bHMWK is comprised of the fragment 1-2 light chain portion; (b) fragment 1-2 or fragment 2 is the binding site to negatively charged surfaces, while the light chain interacts with other components of the surface-mediated reactions; and (c) bovine plasma kallikrein releases kinins, but probably does not cause the release of fragment 1-2 from human HMWK.

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