Platelet aggregation but not activation and degranulation during the acute post-ischemic reperfusion phase in livers with no underlying disease
Journal Title: Journal of Clinical and Translational Research - Year 2015, Vol 1, Issue 2
Abstract
Background: Platelets and P-selectin (CD62P) play an unequivocal role in the pathology of hepatic ischemia/reperfusion (I/R) injury. Inhibition or knock-out of P-selectin or immunodepletion of platelets results in amelioration of post-ischemic inflammation, reduced hepatocellular damage, and improved survival. However, P-selectin expression on platelets and endothelial cells, which concurs with platelet activation, has never been clearly demonstrated in I/R-subjected livers. Aims: To determine whether platelets become activated and degranulate in the acute phase of liver I/R and whether the platelets interact with neutrophils. Methods: Hepatic I/R was induced in male C57BL/6J mice (N = 12) using 37.5-min ischemia time. Platelets, endothelial cells, and neutrophils were fluorescently labeled by systemic administration of non-blocking antibodies. Cell kinetics were monitored by intravital spinning disk confocal microscopy during 90 min of reperfusion. Image analysis and quantification was performed with dedicated software. Results: Platelets adhered to sinusoids more extensively in post-ischemic livers compared to livers not subjected to I/R and formed aggregates, which occurred directly after ischemia. Platelets and endothelial cells did not express P-selectin in post-ischemic livers. There was no interaction between platelets and neutrophils. Conclusions: Platelets aggregate but do not become activated and do not degranulate in post-ischemic livers. There is no platelet neutrophil interplay during the early reperfusion phase in a moderate model of hepatic I/R injury. The mechanisms underlying the biological effects of platelets and P-selectin in this setting warrant further investigation. Relevance for patients: I/R in surgical liver patients may compromise outcome due to post-ischemic oxidative stress and sterile inflammation. Both processes are mediated in part by platelets. Understanding platelet function during I/R is key to developing effective interventions for I/R injury and improving clinical outcomes.
Authors and Affiliations
Rowan F. van Golen, Katarzyna M. Stevens, Pina Colarusso, Hartmut Jaeschke, Michal Heger
Keywords
Related Articles
- EP ID EP678816
- DOI -
- Views 230
- Downloads 0
Limitations of Quantitative Blush Evaluator (QuBE) as myocardial perfusion assessment method on digital coronary angiograms
Background and Aim: Quantitative Blush Evaluator (QuBE) is a software application that allows quantifying myocardial perfusion in coronary angiograms after a percutaneous coronary intervention. QuBE has some limitations...
The impact of sterile inflammation in acute liver injury
Background: The liver has a number of functions in innate immunity. These functions predispose the liver to innate immune-mediated liver injury when inflammation goes unchecked. Significant progress has been made in the...
The effect of human amniotic epithelial cells on urethral stricture fibroblasts
Background: Urethral stricture disease (USD) is effectively managed by buccal mucosa (BM) urethroplasty. Lack of adequate healthy BM has led to the use of autologous tissue-engineered BM grafts. Such grafts are costly, n...
Extrahepatic toxicity of acetaminophen: critical evaluation of the evidence and proposed mechanisms
Research on acetaminophen (APAP) toxicity over the last several decades has focused on the pathophysiology of liver injury, but increasingly attention is paid to other known and possible adverse effects. It has been know...
Making 'null effects' informative: statistical techniques and inferential frameworks
Being able to interpret ‘null effects’ is important for cumulative knowledge generation in science. To draw informative conclusions from null-effects, researchers need to move beyond the incorrect interpretation of a non...