Related Experiment Video
Updated: Jun 29, 2026
10:58
Methods to Study Lipid Alterations in Neutrophils and the Subsequent Formation of Neutrophil Extracellular Traps
Published on: March 29, 2017
Statins alter neutrophil migration by modulating cellular Rho activity--a potential mechanism for statins-mediated
B M Maher1, T Ni Dhonnchu, J P Burke
1University College Dublin School of Medicine and Medical Sciences, UCD Conway Institute and Professor Eoin O'Malley National Centre for Cardiothoracic Surgery, Mater Misericordiae University Hospital, Dublin, Ireland. belinda.maher@ucd.ie
Journal of Leukocyte Biology
|October 9, 2008
Summary
Statins like pravastatin significantly reduce neutrophil migration, a key factor in inflammatory diseases and transplant rejection. This effect stems from statins inhibiting Rho activity, offering a new therapeutic target for controlling excessive inflammation.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Neutrophil migration is crucial for innate immunity but also drives inflammatory diseases and transplant rejection.
- Statins (HMG-CoA reductase inhibitors) show anti-inflammatory potential and improve transplant survival, but their effect on neutrophil function is unclear.
Purpose of the Study:
- To investigate the impact of statins on neutrophil transendothelial migration and elucidate the underlying mechanisms.
Main Methods:
- Assessed the effect of pravastatin, simvastatin, and atorvastatin on neutrophil migration toward fMLP.
- Measured neutrophil adhesion and adhesion molecule expression.
- Investigated the role of Rho signaling pathway activity and geranylgeranyl pyrophosphate rescue.
Main Results:
- Pravastatin, simvastatin, and atorvastatin significantly reduced neutrophil transendothelial migration.
- This reduction was independent of changes in neutrophil adhesion or adhesion molecule expression.
- Statins decreased fMLP-induced Rho activity, which was reversed by geranylgeranyl pyrophosphate.
Conclusions:
- Statins effectively inhibit neutrophil transendothelial migration by reducing Rho activity.
- This mechanism highlights statins as potential therapeutics for inflammatory conditions characterized by excessive neutrophil migration, including allograft rejection.
Related Concept Videos
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
01:21Cell Polarization by Rho Proteins
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:29Cholesterol: Significance and Regulation
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
01:18Role of Myosin in Cell Migration
Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction. It is...
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction. It is...
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
Angina pectoris, a primary symptom of ischemic heart disease, requires careful pharmacological interventions. In this context, calcium channel blockers (CCBs) and ranolazine have emerged as crucial pharmacotherapeutic agents, providing deep insights into the complexities of angina management.
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...