Related Experiment Videos
Human monocyte inflammatory mediator gene expression is selectively regulated by adherence substrates
D F Eierman1, C E Johnson, J S Haskill
1Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill 27599.
Journal of Immunology (Baltimore, Md. : 1950)
|March 15, 1989
Summary
Monocyte inflammatory mediator gene expression depends on substrate interactions. Adherence to collagen uniquely boosted TNF-alpha, while fibronectin and collagen decreased CSF-1, showing substrate selectivity influences monocyte responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Monocytes play a crucial role in inflammation and immune responses.
- Early interactions of monocytes with extracellular matrix components during extravasation prime them for mediator synthesis.
- Previous work showed plastic adherence rapidly alters monocyte inflammatory mediator gene expression.
Purpose of the Study:
- To investigate how monocyte adherence to different extracellular matrix substrates affects inflammatory mediator gene expression.
- To compare the effects of substrate adherence with stimulation by phorbol myristate acetate (PMA) and N-formylmethionyl-leucyl-phenylalanine (FMLP).
Main Methods:
- Monocytes were adhered to surfaces coated with fibronectin, fibronectin/anti-fibronectin complexes, or collagen.
- Steady-state mRNA levels of tumor necrosis factor-alpha (TNF-alpha), colony-stimulating factor-1 (CSF-1), and lysozyme were quantified.
- Non-adherent monocytes were stimulated with PMA or FMLP, and gene expression was analyzed.
Main Results:
- Adherence to fibronectin-coated surfaces yielded TNF-alpha and CSF-1 mRNA levels similar to plastic adherence.
- Adherence to fibronectin or collagen significantly reduced CSF-1 induction and lysozyme expression.
- Monocyte adherence to collagen induced the highest sustained TNF-alpha expression.
- PMA stimulation induced c-fos and TNF-alpha and down-regulated lysozyme mRNA in non-adherent monocytes, but CSF-1 induction varied among donors.
Conclusions:
- Monocyte mediator expression is significantly influenced by the specific signals generated from adherence to different extracellular matrix substrates.
- Substrate selectivity plays a more critical role in modulating monocyte inflammatory responses than the initial chemotactic signal.
- These findings highlight the complex interplay between monocyte-extracellular matrix interactions and inflammatory gene regulation.