Related Experiment Video
Updated: Jul 14, 2026
Laminar Flow-based Assays to Investigate Leukocyte Recruitment on Cultured Vascular Cells and Adherent Platelets
Published on: April 9, 2018
Mobilizing lipocortin 1 in adherent human leukocytes downregulates their transmigration
M Perretti1, J D Croxtall, S K Wheller
1Department of Biochemical Pharmacology, William Harvey Research Institute, London, UK.
Abstract:
Polymorphonuclear leukocyte (PMN) migration into sites of inflammation is fundamental to the host defense response. Activation of endothelial cells and PMNs increases the expression or activation of adhesion molecules, culminating in rolling and subsequent adherence of these cells to the vascular wall. Further activation of adherent PMNs, possibly by endothelial cell ligands, leads, within a few minutes, to extravasation itself. This process is not clearly understood, but adhesion molecules or related proteins, as well as endogenous chemokines, may play an important role. The anti-inflammatory glucocorticoids delay extravasation, which implies that an inhibitory regulatory system exists. Resting PMNs contain abundant cytoplasmic lipocortin 1 (LC1, also called annexin I)', and the activity profile of this protein suggests that it could reduce PMN responsiveness. To investigate this we have assessed neutrophil transmigration both in vivo and in vitro and examined the content and subcellular distribution of LC1 in PMNs by fluorescence-activated cell-sorting (FACS) analysis, western blotting and confocal microscopy. We report that LC1 is mobilized and externalized following PMN adhesion to endothelial monolayers in vitro or to venular endothelium in vivo and that the end point of this process is a negative regulation of PMN transendothelial passage.
Insights
Lipocortin 1 (LC1) is mobilized and externalized from neutrophils upon adhesion, negatively regulating their passage through blood vessel walls during inflammation. This finding reveals a key mechanism in controlling inflammatory cell migration.
Area of Science:
- Immunology
- Cell Biology
- Inflammation Research
Background:
- Polymorphonuclear leukocyte (PMN) migration is crucial for host defense during inflammation.
- Endothelial cell and PMN activation increases adhesion molecules, leading to PMN rolling, adherence, and extravasation.
- Glucocorticoids delay extravasation, suggesting an inhibitory regulatory system exists.
Purpose of the Study:
- To investigate the role of lipocortin 1 (LC1) in regulating PMN transmigration.
- To determine if LC1 mobilization and externalization impact PMN responsiveness during extravasation.
Main Methods:
- Assessed neutrophil transmigration in vivo and in vitro.
- Analyzed LC1 content and subcellular distribution using FACS, western blotting, and confocal microscopy.
- Examined LC1 mobilization and externalization following PMN adhesion to endothelial cells.
Main Results:
- LC1 is mobilized and externalized from PMNs after adhesion to endothelial monolayers (in vitro) and venular endothelium (in vivo).
- This LC1 externalization negatively regulates PMN transendothelial passage.
- The findings suggest LC1 acts as an endogenous inhibitor of PMN extravasation.
Conclusions:
- Lipocortin 1 (LC1) plays a significant inhibitory role in PMN extravasation.
- LC1 mobilization and externalization represent a key regulatory mechanism controlling inflammatory cell migration.
- Understanding LC1's function may offer new therapeutic targets for inflammatory diseases.
Related Concept Videos
01:09Cell Migration
01:31Mechanism of Lamellipodia Formation