MONOCYTE ADHESION TO FIBRONECTIN IN PSORIASIS

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 hex-osaminidase 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.