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Neutrophils contribute to hepatic ischemia-reperfusion injury by a CD18-independent mechanism
L A Langdale1, L C Flaherty, H D Liggitt
1Department of Surgery, University of Washington, Seattle.
Abstract:
Hepatic ischemia-reperfusion injury is reported to be modulated by neutrophils (PMNs). The adhesion and emigration of PMNs that precede tissue inflammation and necrosis in other organs are mediated, in part, by the leukocyte adhesion complex CD11/CD18. In this study, the role of PMN adhesion via CD11/CD18 in isolated liver ischemia-reperfusion injury was examined in rabbits using a blocking monoclonal antibody (mAb 60.3) specific for the CD18 receptor. Vinblastine-induced neutropenia provided significant protection, confirming participation of neutrophils in the pathogenesis of hepatic injury. Inhibition of PMN adherence with mAb 60.3 did not ameliorate injury, as measured by aminotransferase concentrations or a histologic scoring system for injury severity. Histologic sections were scored for pattern and extent of injury as well as neutrophil association with injury. These results suggest a CD18-independent mechanism of neutrophil adhesion in the evolution of isolated hepatic ischemia-reperfusion injury.
Insights
Neutrophils modulate hepatic ischemia-reperfusion injury. However, blocking neutrophil adhesion via CD11/CD18 did not protect the liver, suggesting a CD18-independent mechanism in this injury model.
Area of Science:
- Immunology
- Hepatology
- Surgical Pathology
Background:
- Hepatic ischemia-reperfusion (I/R) injury is a significant clinical challenge.
- Neutrophils (PMNs) play a role in I/R injury, with their adhesion and emigration mediated by the CD11/CD18 complex.
- Understanding PMN adhesion mechanisms is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the role of PMN adhesion via the CD11/CD18 complex in isolated hepatic I/R injury.
- To determine if blocking CD18-mediated adherence with a monoclonal antibody (mAb 60.3) mitigates liver injury.
Main Methods:
- Isolated rabbit liver I/R model.
- Induction of neutropenia using vinblastine.
- Administration of mAb 60.3, specific for the CD18 receptor, to block PMN adherence.
- Assessment of liver injury using aminotransferase levels and histologic scoring.
Main Results:
- Vinblastine-induced neutropenia significantly protected the liver from I/R injury.
- Inhibition of PMN adherence using mAb 60.3 did not reduce aminotransferase concentrations or improve histologic injury scores.
- Histologic analysis showed no significant difference in PMN association with injury between treated and untreated groups.
Conclusions:
- Neutrophil participation is confirmed in hepatic I/R injury pathogenesis.
- CD18-mediated PMN adhesion is not the primary mechanism driving liver injury in this model.
- A CD18-independent pathway likely mediates neutrophil adhesion during hepatic I/R injury.