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Mini-plasminogen like molecule in septic patients
L C Kordich1, V P Porterie, O Lago
1Departament of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Abstract:
Plasma from 7 septic patients with positive blood cultures were studied. None of them presented either clinical or laboratory evidence of Disseminated Intravascular Coagulation. The white cells count varied between 5 and 45 X 10(9)/l. In plasma functional plasminogen levels varied between 25 and 45%, while those of alpha 2-antiplasmin were normal (80-105%). The levels of elastase ranged between 250 and 750 micrograms/ml. Leukocyte elastase digests plasminogen "in vitro" and is able to produce several fragments; one of them called mini-plasminogen lacking lysine binding sites; therefore it does not bind to lysine-Sepharose 4B. Two different behaviors were observed in the plasmatic plasminogen of these patients with respect to their binding capacity to lysine-Sepharose 4 B. 3 patients had plasminogen which did not bind to lysine-Sepharose 4 B; the other 4 had two different components, one of which bound to lysine-Sepharose 4 B and another one which did not bind. Previous studies "in vitro" have shown that leukocyte elastase modifies alpha 2-antiplasmin, initially producing a non-plasminogen binding form. A free alpha 2-antiplasmin (non-plasminogen binding form) was detected in the plasma of these patients with sepsis by crossed immunoelectrophoresis with plasminogen in the first dimension. It seems tenable that high levels of leukocyte elastase could be responsible for these findings although, the possible relationships to leukocyte elastase still remain to be proven but could possibly explain this effect.
Insights
High leukocyte elastase in sepsis patients alters plasminogen, creating forms that do not bind to lysine-Sepharose. This suggests elastase may modify key proteins in sepsis, impacting coagulation and fibrinolysis pathways.
Area of Science:
- Biochemistry
- Hematology
- Clinical Medicine
Background:
- Sepsis is a life-threatening condition characterized by a dysregulated host response to infection.
- Disseminated Intravascular Coagulation (DIC) is a common complication of sepsis, but its absence does not preclude other hemostatic abnormalities.
- Leukocyte elastase is a serine protease released by neutrophils, known to degrade various proteins, including components of the fibrinolytic system.
Purpose of the Study:
- To investigate the impact of sepsis on plasminogen and alpha 2-antiplasmin functionality in patients without DIC.
- To explore the potential role of leukocyte elastase in modifying these proteins during sepsis.
- To assess the binding behavior of patient plasminogen to lysine-Sepharose 4B as an indicator of functional alteration.
Main Methods:
- Plasma samples were collected from 7 septic patients with positive blood cultures and no clinical or laboratory evidence of DIC.
- Functional plasminogen and alpha 2-antiplasmin levels were measured.
- Leukocyte elastase levels were quantified.
- Plasminogen binding capacity to lysine-Sepharose 4B was assessed.
- Crossed immunoelectrophoresis with plasminogen was used to detect free alpha 2-antiplasmin.
Main Results:
- Septic patients without DIC exhibited reduced functional plasminogen levels (25-45%) with normal alpha 2-antiplasmin (80-105%).
- Elevated leukocyte elastase levels (250-750 µg/ml) were observed.
- Plasminogen from 3 patients did not bind to lysine-Sepharose 4B, while plasma from the other 4 contained both binding and non-binding plasminogen components.
- A non-plasminogen binding form of alpha 2-antiplasmin was detected in patient plasma.
Conclusions:
- Elevated leukocyte elastase in sepsis may lead to the formation of modified plasminogen, characterized by a lack of lysine binding sites.
- Leukocyte elastase may also modify alpha 2-antiplasmin, rendering it unable to bind plasminogen.
- These findings suggest that leukocyte elastase plays a significant role in the hemostatic abnormalities observed in sepsis, even in the absence of DIC.