Related Experiment Videos
Migration of monocytes across endothelium and passage through extracellular matrix involve separate molecular domains
1Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York 10021-6399, USA.
Abstract:
During the inflammatory response, the adhesion molecule PECAM plays a crucial role in transendothelial migration, the passage of leukocytes across endothelium. We report here an additional role for PECAM in the subsequent migration of monocytes through the subendothelial extracellular matrix. PECAM has six immunoglobulin (Ig) superfamily domains. Monoclonal antibodies whose epitopes map to domains 1 and/or 2 selectively block monocyte migration through the endothelial junction, whereas those that map to domain 6 block only the migration through the extracellular matrix, trapping the monocyte between the endothelium and its basal lamina. Therefore, transendothelial migration (diapedesis) and passage through extracellular matrix (interstitial migration) are distinct and separable phases of monocyte emigration. Furthermore, distinct and separate Ig domains of PECAM are involved in mediating these two steps.
Insights
Platelet endothelial cell adhesion molecule (PECAM) guides monocytes during inflammation. Different domains of PECAM mediate distinct steps in monocyte migration, including crossing the endothelium and moving through the extracellular matrix.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Inflammation involves leukocyte migration across endothelium.
- Platelet endothelial cell adhesion molecule (PECAM) is vital for leukocyte transendothelial migration.
- PECAM is a key adhesion molecule with six immunoglobulin (Ig) superfamily domains.
Purpose of the Study:
- To investigate the role of PECAM in monocyte migration beyond transendothelial passage.
- To determine if different domains of PECAM mediate distinct phases of monocyte emigration.
- To differentiate the mechanisms of endothelial transmigration and extracellular matrix penetration by monocytes.
Main Methods:
- Utilized monoclonal antibodies targeting specific PECAM domains (1, 2, and 6).
- Assessed the impact of these antibodies on monocyte migration through endothelial monolayers.
- Evaluated monocyte passage through the subendothelial extracellular matrix.
Main Results:
- Antibodies targeting PECAM domains 1 and/or 2 blocked monocyte migration through the endothelium.
- Antibodies targeting PECAM domain 6 specifically inhibited migration through the extracellular matrix.
- These findings demonstrate that transendothelial migration (diapedesis) and interstitial migration are separable processes mediated by distinct PECAM domains.
Conclusions:
- PECAM mediates distinct functions in monocyte emigration.
- Different immunoglobulin domains of PECAM are responsible for mediating transendothelial migration and extracellular matrix penetration.
- This highlights the complex, multi-step role of PECAM in inflammatory cell trafficking.