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Published on: May 21, 2018
Expression of beta 2-integrins and L-selectin on polymorphonuclear leukocytes in septic patients
M Thiel1, C Zourelidis, J D Chambers
1Department of Anaesthesiology, University of Munich, Germany.
Abstract:
Adhesion molecules on polymorphonuclear leukocytes (PMNL) play an important role in nonspecific defense mechanisms directed at invading microorganisms. When local infection, however, cannot be controlled, a systemic inflammatory response syndrome (SIRS) ensues which may progress to septic shock and multiple organ failure, these being major determinants of the patient's outcome. In the present study, the expression of beta 2-integrins and L-selectin on blood PMNL was measured on subsequent days in patients with sepsis (n = 17) and in healthy volunteers (n = 15). beta 2-Integrins and L-selectin molecules were detected by flow cytometry, using the monoclonal antibodies IB4 (anti-CD18) and Dreg200 (anti-CD62L), respectively. Adhesion molecules were determined at baseline immediately after blood collection and also 45 min after incubation of cells in vitro at body temperature to allow for spontaneous regulation. In addition, PMNL were activated by receptor-dependent and receptor-independent stimuli to characterize stimulus-specific adhesion molecule expression. In parallel with the measurement of adhesion molecules, severity of sepsis was assessed by the Elebute score. The results demonstrate significant differences in the basal, spontaneous and stimulus-induced expression of adhesion molecules between healthy volunteers, survivors (n = 11) and nonsurvivors (n = 6). Moreover, when survivors and nonsurvivors with severe sepsis (Elebute score > 12) were compared, basal expressions of both beta 2-integrins and L-selectin were significantly lower in patients who did not survive. Thus, measurement of adhesion molecules on circulating PMNL may be useful to identify septic patients at high risk for lethal outcome.
Insights
Low expression of adhesion molecules like beta 2-integrins and L-selectin on polymorphonuclear leukocytes (PMNL) in sepsis patients indicates a higher risk of mortality. Measuring these molecules can help identify high-risk individuals for better sepsis management.
Area of Science:
- Immunology
- Critical Care Medicine
- Molecular Biology
Background:
- Polymorphonuclear leukocytes (PMNL) express adhesion molecules crucial for fighting infections.
- Systemic Inflammatory Response Syndrome (SIRS) and septic shock can lead to organ failure and poor patient outcomes.
- Understanding PMNL adhesion molecule expression is vital for predicting sepsis severity.
Purpose of the Study:
- To investigate the expression levels of beta 2-integrins and L-selectin on blood PMNL in sepsis patients.
- To correlate adhesion molecule expression with sepsis severity and patient survival.
- To evaluate the potential of adhesion molecule measurement as a prognostic tool in sepsis.
Main Methods:
- Flow cytometry was used to quantify beta 2-integrins (CD18) and L-selectin (CD62L) on PMNL from sepsis patients and healthy volunteers.
- Adhesion molecule expression was measured at baseline, after in vitro incubation, and following stimulation.
- Sepsis severity was assessed using the Elebute score.
Main Results:
- Significant differences in basal, spontaneous, and stimulus-induced adhesion molecule expression were observed between healthy individuals, survivors, and nonsurvivors.
- Patients with severe sepsis (Elebute score > 12) who did not survive showed significantly lower basal expression of both beta 2-integrins and L-selectin.
- These findings highlight distinct adhesion molecule profiles associated with sepsis outcomes.
Conclusions:
- Basal expression levels of beta 2-integrins and L-selectin on circulating PMNL differ between sepsis survivors and nonsurvivors.
- Lower expression of these adhesion molecules in severe sepsis patients is linked to a higher risk of mortality.
- Measuring PMNL adhesion molecules may serve as a valuable biomarker for identifying septic patients at high risk of a lethal outcome.
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