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CD40 expression and function on human dermal microvascular endothelial cells: role in cutaneous inflammation
S R Singh1, K Casper, S Summers
1Department of Dermatology, Emory University, Atlanta, Georgia, USA. srsingh@emory.edu
Clinical and Experimental Dermatology
|August 8, 2001
Summary
CD40 is expressed on human dermal microvascular endothelial cells (HDMEC) and its expression is upregulated by inflammatory cytokines. CD40 signaling promotes leukocyte adhesion, indicating its role in skin inflammation.
Area of Science:
- Immunology
- Cell Biology
- Dermatology
Background:
- CD40 is a TNF receptor superfamily member involved in immune cell interactions.
- CD40 is expressed on endothelial cells, but its role in microvascular endothelium is not fully understood.
Purpose of the Study:
- To investigate CD40 expression and function on human dermal microvascular endothelial cells (HDMEC).
- To determine the effect of proinflammatory cytokines on CD40 expression in HDMEC.
- To elucidate the role of CD40 in leukocyte adhesion to HDMEC.
Main Methods:
- HDMEC culture and stimulation with TNF-alpha and IFN-gamma.
- Flow cytometry to assess CD40 expression.
- Recombinant CD40 ligand stimulation and analysis of adhesion molecule expression (E-selectin, ICAM, VCAM).
- Leukocyte adhesion assays using Jurkat cells.
Main Results:
- HDMEC express CD40, with increased expression upon stimulation with TNF-alpha and IFN-gamma.
- CD40 engagement enhances E-selectin induction on HDMEC.
- IFN-gamma stimulation increases Jurkat leukocyte binding to HDMEC via a CD40-CD154 dependent pathway.
- No significant effect on ICAM or VCAM expression was observed.
Conclusions:
- CD40 expression on HDMEC is regulated by proinflammatory cytokines.
- CD40 signaling in HDMEC contributes to leukocyte recruitment, suggesting a role in cutaneous inflammation.