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Monocyte modulation of endothelial leukocyte adhesion molecules
D Weill1, J L Wautier, C Dosquet
1Laboratoire de Biologie Vasculaire et Cellulaire, Université de Paris VII, France.
The Journal of Laboratory and Clinical Medicine
|June 1, 1995
Summary
Monocyte-conditioned medium influences endothelial adhesion molecules differently than recombinant cytokines. This affects leukocyte adhesion, with interleukin-1 beta playing a significant role.
Area of Science:
- Immunology
- Cell Biology
- Endothelial Biology
Background:
- Leukocyte adhesion to endothelium is crucial for immune responses.
- Cytokines like interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) upregulate endothelial adhesion molecules.
- Monocytes release factors that can modulate endothelial cell behavior.
Purpose of the Study:
- To investigate the impact of monocyte-conditioned medium (MCM) and recombinant cytokines on endothelial adhesion receptor expression.
- To compare the effects of MCM versus individual cytokines (IL-1 beta, TNF-alpha) on E-selectin, VCAM-1, and ICAM-1.
- To determine the role of TNF-alpha and IL-1 beta in MCM-induced changes in adhesion molecules and monocyte adhesion.
Main Methods:
- Culturing monocytes with and without pentoxifylline to generate conditioned media.
- Treating endothelial cells with MCM, recombinant IL-1 beta, and TNF-alpha.
- Measuring the expression of E-selectin, VCAM-1, and ICAM-1 on endothelial cells.
- Assessing monocyte adhesion to treated endothelial cells.
- Utilizing neutralizing antibodies against TNF-alpha and IL-1 beta.
Main Results:
- MCM, IL-1 beta, and TNF-alpha similarly induced E-selectin expression.
- TNF-alpha was more potent than MCM in inducing VCAM-1 and ICAM-1.
- Pentoxifylline inhibited TNF-alpha production in MCM.
- Neutralizing TNF-alpha or IL-1 beta significantly reduced MCM's effect on E-selectin and monocyte adhesion.
- IL-1 beta neutralization had a more substantial impact on monocyte adhesion than TNF-alpha inhibition.
Conclusions:
- Adherent monocytes release cytokines and antagonists that differentially affect endothelial adhesion receptors compared to recombinant cytokines.
- E-selectin and ICAM-1 expression are modulated by monocyte-derived factors, influencing leukocyte adhesion.
- IL-1 beta and TNF-alpha are key mediators in the MCM-induced modulation of endothelial adhesion molecules and monocyte adhesion.