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E-selectin expression and stimulation by inflammatory mediators are developmentally regulated during embryogenesis.
D S Milstone1, P E O'Donnell, G Stavrakis
1Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. milstone@rascal.med.harvard.edu
Summary
The study reveals distinct developmental stages for endothelial adhesion molecule expression during embryogenesis. E-selectin inducibility emerges later than intercellular adhesion molecule-1 (ICAM-1), indicating differential regulation in developing blood vessels.
Area of Science:
- Developmental Biology
- Immunology
- Vascular Biology
Background:
- Leukocyte recruitment during inflammation depends on endothelial adhesion molecules.
- E-selectin and ICAM-1 are key adhesion molecules involved in inflammatory responses.
- Understanding their developmental regulation is crucial for comprehending immune cell trafficking in embryos.
Purpose of the Study:
- To investigate the developmental onset of E-selectin and ICAM-1 expression and inducibility.
- To analyze the ontogeny of endothelial adhesion molecule expression in murine embryos and embryoid bodies (EB).
- To identify distinct stages in the development of E-selectin inducibility.
Main Methods:
- Studied murine embryos at various developmental stages (E9.5-E13.5).
- Utilized embryoid bodies (EB) derived from embryonic stem cells to model early endothelial development.
- Assessed basal and induced expression of E-selectin and ICAM-1 using inflammatory mediators and endotoxin.
Main Results:
- E-selectin and ICAM-1 exhibit differential regulation during development.
- Three distinct stages characterize the ontogeny of E-selectin inducibility.
- ICAM-1 inducibility is present earlier than E-selectin inducibility in both embryos and EB.
- Embryos are protected from maternal inflammatory insults.
- E-selectin expression is inducible starting from embryonic day 12.5-13.5.
Conclusions:
- The acquisition of E-selectin inducibility is a developmentally regulated process.
- This regulation likely involves changes in signal transduction, transcription factors, and chromatin accessibility.
- Specific endothelial subpopulations may exhibit restricted inducibility of E-selectin.