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Leukocyte activation with increased expression of CR3 receptors during cardiopulmonary bypass
Y J Gu1, W van Oeveren, P W Boonstra
1Thorax Centre, University Hospital Groningen, The Netherlands.
Insights
Cardiopulmonary bypass (CPB) increases leukocyte complement receptor type 3 (CR3) expression, particularly early and late in the procedure. This suggests CR3 plays a role in CPB-related inflammation, potentially offering a therapeutic target.
Area of Science:
- Cardiovascular Surgery
- Immunology
- Inflammation Research
Background:
- Cardiopulmonary bypass (CPB) is essential for cardiac surgery but can trigger inflammatory responses.
- Leukocyte adhesion molecules, such as complement receptor type 3 (CR3), are implicated in CPB-induced inflammation.
Purpose of the Study:
- To investigate the dynamic changes in CR3 expression on leukocytes during CPB.
- To explore the potential mechanisms and implications of altered CR3 expression in CPB.
Main Methods:
- Blood samples were collected from 16 patients undergoing CPB at various time points.
- Leukocyte CR3 expression was quantified using time-resolved fluoroimmunoassay.
- In vitro studies assessed CR3 expression in response to zymosan-activated plasma.
Main Results:
- CR3 expression significantly increased immediately after CPB initiation, correlating with elevated C3a levels.
- A second peak in CR3 expression occurred post-aortic cross-clamp release, coinciding with increased leukotriene B4 and elastase.
- In vitro data suggested complement activation mediates the early rise in CR3 expression.
Conclusions:
- CPB induces biphasic increases in leukocyte CR3 expression.
- Complement activation likely drives the initial CR3 upregulation.
- Targeting CR3 may mitigate CPB-associated leukocyte-mediated complications.
Abstract:
The effects of cardiopulmonary bypass (CPB) on the expression of leukocyte adhesive receptors, ie, complement receptor type 3 (CR3), were studied in 16 patients. The CR3 expression on leukocytes was determined by time-resolved fluoroimmunoassay on a standardized number of cells isolated from blood samples taken during various times during CPB. The results demonstrated that CR3 expression on leukocytes increased immediately after the start of CPB (p less than 0.05), concomitant with an early sharp increase of plasma concentrations of C3a (p less than 0.01). After release of the aortic cross-clamp, a second peak of leukocyte CR3 expression was induced (p less than 0.05), paralleled by a significant increase of leukotriene B4 (p less than 0.05) and elastase (p less than 0.05) levels in the late period of CPB. In vitro studies with leukocytes isolated from healthy donors (n = 5) showed a dose-dependent increase of CR3 expression stimulated by zymosan-activated plasma, indicating that the rapid CR3 expression on leukocytes is likely mediated by complement activation. However, the mechanisms for the second peak of leukocyte CR3 expression during CPB remain to be further elucidated. In conclusion, CR3 expression on leukocytes increased immediately after the start of CPB and was followed by a second peak of expression in the late phase of CPB. Pharmacological blockage of these adhesive receptors might reduce the leukocyte-mediated deleterious effects of CPB.