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Prekallikrein activation in the adult respiratory distress syndrome
Insights
Prekallikrein activation was significantly higher in patients with adult respiratory distress syndrome (ARDS). This supports the role of plasma kallikrein in ARDS pathogenesis.
Area of Science:
- Biochemistry
- Hematology
- Critical Care Medicine
Background:
- Prekallikrein is the inactive precursor to plasma kallikrein, a key enzyme in the contact system.
- Plasma kallikrein participates in blood coagulation, fibrinolysis, and kinin formation.
- The role of prekallikrein activation in adult respiratory distress syndrome (ARDS) is not well understood.
Purpose of the Study:
- To determine if prekallikrein is activated in patients with ARDS.
- To investigate the interaction of activated plasma kallikrein with C1-inhibitor in ARDS patients.
Main Methods:
- Plasma samples from 12 critically ill patients (5 with ARDS) were analyzed.
- Prekallikrein activation was assessed using the ratio of functional prekallikrein to prekallikrein-kallikrein antigen.
- Modification of C1-inhibitor was examined as an indicator of reaction with kallikrein.
Main Results:
- Prekallikrein was extensively activated in ARDS patients compared to non-ARDS critically ill patients.
- Modified C1-inhibitor, indicating reaction with kallikrein, was detected in ARDS patients but not in others.
- These findings confirm prekallikrein activation in ARDS.
Conclusions:
- Prekallikrein is activated in the plasma of critically ill patients with ARDS.
- Plasma kallikrein-mediated reactions, including bradykinin release and neutrophil activation, may contribute to ARDS pathogenesis.
- C1-inhibitor modification provides further evidence for kallikrein activity in ARDS.
Abstract:
Prekallikrein is the zymogen form of plasma kallikrein, a proteolytic enzyme of the contact system of blood coagulation, fibrinolysis and kinin formation. To assess whether prekallikrein was activated in the adult respiratory distress syndrome (ARDS), we examined plasma samples from 12 critically ill patients including five individuals with ARDS. Using the ratio between functional prekallikrein and prekallikrein-kallikrein antigen as an index for prekallikrein activation, we found that prekallikrein was extensively activated in patients with ARDS, while this was significantly less in the case of critically ill patients without ARDS. Following activation of prekallikrein in plasma, kallikrein reacts with its substrates and with protease inhibitors, among which the alpha 2-glycoprotein C1-inhibitor. Thus, we examined whether C1-inhibitor of critically ill individuals was modified in a way suggesting that it had reacted with kallikrein. Such a modification was found in the five patients with ARDS, while it was not detectable in the seven patients without ARDS. This observation further confirmed the activation of prekallikrein in patients with ARDS. We suggest that plasma kallikrein-mediated reactions, which include bradykinin release and neutrophil activation, may contribute to the pathogenesis of ARDS.