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Neutrophils from MMP-9- or neutrophil elastase-deficient mice show no defect in transendothelial migration under flow
Jennifer R Allport1, Yaw-Chyn Lim, J Michael Shipley
1Vascular Research Division, Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.
Abstract:
Recent evidence has suggested a role for neutrophil proteases during certain inflammatory responses. We demonstrated previously that neutrophil proteases can degrade components of the adherens junctions during neutrophil-endothelial adhesion. We tested the hypothesis that degradation of VE-cadherin at lateral junctions by elastase or MMP-9 facilitates neutrophil transendothelial migration. Neutrophils from MMP-9 or elastase null mice and strain-matched control mice expressed high levels of LFA-1, Mac-1, and L-selectin on their cell surface. Under flow conditions, wild-type and deficient neutrophils rolled, arrested, and transmigrated activated murine endothelium. There was no difference in the total numbers of interacting neutrophils or in the percentage of transmigrated cells. In addition, deficient neutrophils remained capable of degrading murine endothelial VE-cadherin. These results indicate that although neutrophil proteases may play a role in the acute inflammatory response, neutrophil elastase or MMP-9 is not essential for neutrophil transendothelial migration in this murine system.
Insights
Neutrophil proteases like elastase and MMP-9 do not appear essential for neutrophils migrating through blood vessels. Studies show these enzymes are not required for neutrophil transendothelial migration in mice.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Neutrophil proteases are implicated in inflammatory responses.
- Neutrophil proteases can degrade adherens junction components during adhesion.
- The role of specific proteases in neutrophil transmigration is not fully understood.
Purpose of the Study:
- To test if elastase or MMP-9 degradation of VE-cadherin facilitates neutrophil transendothelial migration.
- To investigate the necessity of neutrophil elastase and MMP-9 for neutrophil transmigration.
Main Methods:
- Utilized neutrophils from elastase or MMP-9 null mice and wild-type controls.
- Assessed neutrophil adhesion molecules (LFA-1, Mac-1, L-selectin) expression.
- Studied neutrophil-endothelial interactions and transmigration under flow conditions.
- Evaluated the capacity of deficient neutrophils to degrade endothelial VE-cadherin.
Main Results:
- Neutrophils from null mice and controls showed similar expression of key adhesion molecules.
- No significant differences were observed in neutrophil rolling, arrest, or transmigration percentages between wild-type and deficient neutrophils.
- Neutrophils lacking elastase or MMP-9 retained the ability to degrade murine endothelial VE-cadherin.
Conclusions:
- Neutrophil elastase and MMP-9 are not essential for neutrophil transendothelial migration in this murine model.
- While neutrophil proteases may contribute to acute inflammation, their absence does not prevent neutrophil migration across the endothelium.