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Microangiectasias: structural regulators of lymphocyte transmigration.
Timothy W Secomb1, Moritz A Konerding, Charles A West
1Department of Physiology, University of Arizona, Tucson, AZ 85724, USA.
Summary
Lymphocyte migration during inflammation is facilitated by microangiectasias, which reduce mechanical forces. These vessel changes prepare the microcirculation for immune cell transmigration.
Area of Science:
- Immunology
- Microcirculation physiology
- Cellular mechanics
Background:
- Lymphocyte migration into inflamed tissues involves overcoming blood flow forces.
- The prevailing hypothesis suggests multistep adhesive interactions between lymphocytes and endothelial cells.
- Recent findings challenge this by showing high in vivo wall shear stress and low in vitro adhesion.
Purpose of the Study:
- To investigate the mechanisms underlying lymphocyte migration in inflammatory conditions.
- To challenge the traditional hypothesis of lymphocyte-endothelial adhesion under high shear stress.
- To explore the role of microvascular structural adaptations in facilitating lymphocyte transmigration.
Main Methods:
- In vivo and in vitro studies of lymphocyte-endothelial interactions.
- Measurement of wall shear stress in the microcirculation.
- Induction and observation of microangiectasias during inflammation.
Main Results:
- Lymphocyte slowing and transmigration are associated with microangiectasias.
- Microangiectasias, focal dilatations of microvessel segments, are inducible within 4 days of inflammation onset.
- These structures cause a >10-fold local reduction in wall shear stress.
Conclusions:
- Microangiectasias represent a critical adaptation in the inflammatory microcirculation.
- These structural changes reduce mechanical forces, facilitating lymphocyte transmigration.
- A preparatory step to transmigration involves microvascular remodeling, not solely adhesive interactions.