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Monocyte adhesion to fibronectin in psoriasis
G Rein1, A Abraham, S P Raychadauri
1Psoriasis Research Institute, Palo Alto, California 94301.
Background:
After vascular extravasation, mononuclear cells (MNC) undergo chemotaxis and adhesion to extracellular matrix proteins, resulting in their differentiation into macrophages. Although endothelial adhesion and chemotaxis are altered in psoriasis, MNC adhesion to extracellular matrix proteins has not been previously studied in the disease. Since MNC adhesion to endothelial cells is abnormally regulated in psoriasis by TGF-beta, we tested they hypothesis that in psoriasis substance P also regulates the adhesion of monocytes to the extracellular matrix protein fibronectin.
Methods:
Monocytes from 16 normal controls and 11 psoriatic individuals were isolated and purified using a two-step gradient centrifugation procedure. Adhesion to fibronectin was studied by plating monocyte suspensions onto fibronectin-precoated microtiter plates. The number of adherent cells was quantified by measuring their hexosaminidase activity.
Results:
Although statistically significant differences in the basal (unstimulated) adhesion or in the substance P-stimulated adhesion between normal control monocytes and those obtained from psoriatic individuals were not observed, a subpopulation of psoriatics was identified who responded to substance P. Furthermore, this in vitro response to substance P was correlated with the clinical status of the subpopulation which was characterized by unstable psoriasis triggered by stressful life events.
Conclusions:
The results of this study indicate that priming of monocytes by the extracellular matrix protein fibronectin or by elevated levels of substance P are not critical steps in the pathogenesis of stable, chronic psoriasis. Substance P may contribute to the appearance of new lesions in some individuals with unstable psoriasis.
Insights
Substance P may contribute to new psoriasis lesions in unstable cases, but monocyte adhesion to fibronectin isn't a key factor in chronic psoriasis. This study explored monocyte adhesion in psoriasis patients.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Mononuclear cells (MNC) differentiate into macrophages after extravasation, involving chemotaxis and adhesion to extracellular matrix proteins.
- Endothelial adhesion and chemotaxis are altered in psoriasis, but MNC adhesion to extracellular matrix proteins remains unstudied.
- Transforming growth factor-beta (TGF-beta) abnormally regulates MNC adhesion to endothelial cells in psoriasis.
Purpose of the Study:
- To investigate the role of substance P in regulating monocyte adhesion to fibronectin in psoriasis.
- To test the hypothesis that substance P influences monocyte-fibronectin interactions in psoriatic individuals.
Main Methods:
- Monocytes were isolated from 16 healthy controls and 11 psoriatic patients using gradient centrifugation.
- Monocyte adhesion to fibronectin was assessed using fibronectin-coated microtiter plates.
- Adherent cell numbers were quantified by measuring hexosaminidase activity.
Main Results:
- No significant differences in basal or substance P-stimulated monocyte adhesion were found between normal and psoriatic individuals.
- A subset of psoriatic patients showed a response to substance P.
- This in vitro response correlated with unstable psoriasis linked to stressful life events.
Conclusions:
- Monocyte priming by fibronectin or substance P is not critical in the pathogenesis of stable, chronic psoriasis.
- Substance P may play a role in the development of new lesions in some patients with unstable psoriasis.
- The findings suggest a potential link between substance P, monocyte behavior, and the exacerbation of psoriasis in specific patient subgroups.