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Released granulocytic elastase: an indicator of pathobiochemical alterations in septicemia after abdominal surgery
Abstract:
To discover the role of lysosomal enzyme release from polymorphonuclear (PMN) leukocytes during septicemia, plasma levels of PMN elastase were measured with a newly developed enzyme-linked immunosorbent assay for detection of the PMN elastase-alpha 1-proteinase inhibitor complex (E-alpha 1PI). Plasma samples from 41 patients were assayed continuously before and after major abdominal surgery. The patients were divided into a group without infection (group A) and two septicemia groups (survivors in group B and nonsurvivors in group C). The E-alpha 1PI levels of the 11 patients in group A without any signs of pre- or postoperative infection were in the normal range (a normal value of 86.5 +/- 25.5 ng/ml has been reported in 153 healthy subjects), except for a small increase to 208.8 +/- 25.6 ng/ml 12 hours after surgery. When septicemia was confirmed clinically in patients in groups B and C, the E-alpha 1PI levels rose on average to six times the norm in group B (649.9 +/- 116.3 ng/ml) and to more than 10 times the norm in group C (985.0 +/- 154.6 ng/ml). Peak values greater than 2,200 ng/ml could be measured in both groups. In patients in group B, the E-alpha 1PI levels returned to normal during recovery, while in those in group C they remained significantly elevated (560.5 +/- 174.7 ng/ml) until death. Correlations were demonstrated between the amount of elastase released into the circulation and the decrease in the activities of antithrombin III, coagulation factor XIII, and alpha 2-macroglobulin, as well as the increased C-reactive protein in plasma. We conclude that release of elastase and other lysosomal factors from PMN cells plays a major role in the pathobiochemical alterations during septicemia. In addition, significantly elevated E-alpha 1PI levels in the postoperative course seem to be a suitable indicator for onset and persistance of sepsis as well as of the severity of this disorder in patients after major surgery.
Insights
Elevated polymorphonuclear (PMN) elastase levels indicate severe septicemia. Measuring PMN elastase-alpha 1-proteinase inhibitor complex (E-alpha 1PI) in plasma can predict sepsis onset, persistence, and severity after surgery.
Area of Science:
- Biochemistry
- Immunology
- Critical Care Medicine
Background:
- Sepsis is a life-threatening condition characterized by a dysregulated host response to infection.
- Polymorphonuclear (PMN) leukocytes play a crucial role in the inflammatory response during sepsis.
- Lysosomal enzyme release from PMNs contributes to the pathogenesis of sepsis.
Purpose of the Study:
- To investigate the role of lysosomal enzyme release from PMN leukocytes during septicemia.
- To assess plasma levels of PMN elastase-alpha 1-proteinase inhibitor complex (E-alpha 1PI) as a biomarker for sepsis.
- To correlate E-alpha 1PI levels with clinical outcomes in patients undergoing major abdominal surgery.
Main Methods:
- Developed a novel enzyme-linked immunosorbent assay (ELISA) to detect E-alpha 1PI complex.
- Continuously monitored plasma E-alpha 1PI levels in 41 patients before and after major abdominal surgery.
- Categorized patients into non-infected, septic survivor, and septic non-survivor groups.
Main Results:
- Non-infected patients showed normal E-alpha 1PI levels, with a transient increase post-surgery.
- Septic patients exhibited significantly elevated E-alpha 1PI levels, with non-survivors showing higher concentrations than survivors.
- Elevated E-alpha 1PI levels correlated with decreased antithrombin III, factor XIII, alpha 2-macroglobulin, and increased C-reactive protein.
- E-alpha 1PI levels returned to normal in survivors but remained high in non-survivors.
Conclusions:
- PMN elastase release is a major contributor to the pathobiochemical alterations observed in septicemia.
- Plasma E-alpha 1PI levels serve as a sensitive indicator for sepsis onset, persistence, and severity in postoperative patients.
- This biomarker aids in monitoring disease progression and patient prognosis following major surgery.