Porcine high molecular weight kininogen: its purification and properties as a thiol proteinase inhibitor as compared to human high molecular weight kininogen

α1-Proteinase inhibitor (α1-PI) is a natural serine protease inhibitor. Although mainly thought to protect the airways from neutrophil elastase, α1-PI may also regulate the development of airway hyperresponsiveness (AHR), as indicated by our previous findings of an inverse relationship between lung α1-PI activity and the severity of antigen-induced AHR. Because allergic stimulation of the airways causes release of elastase, tissue kallikrein, and reactive oxygen species (ROS), all of which can reduce α1-PI activity and contribute to AHR, we hypothesized that administration of exogenous α1-PI should protect against pathophysiological airway responses caused by these agents. In untreated allergic sheep, airway challenge with elastase, xanthine/xanthine oxidase (which generates ROS), high-molecular-weight kininogen, the substrate for tissue kallikrein, and antigen resulted in bronchoconstriction. ROS and antigen also induced AHR to inhaled carbachol. Treatment with 10 mg of recombinant α1-PI (rα1-PI) blocked the bronchoconstriction caused by elastase, high-molecular-weight kininogen, and ROS, and the AHR induced by ROS and antigen. One milligram of rα1-PI was ineffective. These are the first in vivo data demonstrating the effects of rα1-PI. Our results are consistent with and extend findings obtained with human plasma-derived α1-PI and suggest that α1-PI may be important in the regulation of airway responsiveness.

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Isolation of a human cDNA for .alpha.2-thiol proteinase inhibitor and its identity with low molecular weight kininogen

Biochemistry ◽

10.1021/bi00319a005 ◽

1984 ◽

Vol 23 (24) ◽

pp. 5691-5697 ◽

Cited By ~ 175

Author(s):

Iwao Ohkubo ◽

Kotoku Kurachi ◽

Toshihide Takasawa ◽

Hiroyuki Shiokawa ◽

Makoto Sasaki

Keyword(s):

Molecular Weight ◽

Proteinase Inhibitor ◽

Low Molecular Weight ◽

Human Cdna ◽

Thiol Proteinase Inhibitor ◽

Thiol Proteinase

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The Contact Phase of Blood Coagulation in Diabetes Mellitus and in Patients with Vasculopathy

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661181 ◽

1984 ◽

Vol 52 (03) ◽

pp. 221-223 ◽

Cited By ~ 7

Author(s):

M Christe ◽

P Gattlen ◽

J Fritschi ◽

B Lämmle ◽

W Berger ◽

...

Keyword(s):

Diabetes Mellitus ◽

Molecular Weight ◽

Blood Coagulation ◽

High Molecular Weight ◽

Negative Correlation ◽

Factor Xii ◽

C1 Inhibitor ◽

High Molecular Weight Kininogen ◽

Contact Phase ◽

Α2 Macroglobulin

SummaryThe contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also α2-macroglobulin are significantly elevated in diabetics with complications, for α1-macroglobulin especially in patients with nephropathy, 137.5% ± 36.0 (p <0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 ± 22.1 (p <0.01).Prekallikrein (PK) is increased in all patients’ groups (Table 2) as compared to normals. PK is particularly high (134% ± 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.

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