Modulation of PECAM-1 (CD31] expression in human endothelial cells: Effectof IFN gamma and IL-10

Contacts formed between endothelial cells (EC) permit the formation of a co nfluent monolayer and play a major role in the recruitment and the migratio n of leukocytes in the inflammatory response. It is currently accepted that cytokines are responsible for the signals involved in the induction of suc h endothelial alterations. The platelet EC adhesion molecule (PECAM-1), a s pecific component of EC junctions, is one of many molecules which participa te in the regulation of EC interaction with blood components. Given that th e regulatory mechanisms wh ich affect the expression of th is adhesion mole cule are only partially understood, the aim of the present study was to com pare the effects of two antagonistic inflammatory cytokines, interferon (IF N)-gamma and interleukin IL-10, on the expression of PECAM-1. Human umbilic al vein EC grown to subconfluence were stimulated with IL-10 (10 ng/ml) and /or IFN gamma (100 U/ml) for 24 h. PECAM-1 expression was determined by FAC Scan and immunofluorescence. Morphological analysis of the cell cultures wa s performed by optical and scanning electron microscopy. In the presence of IL-10, no changes in cell growth and morphology or in the intensity of PEC AM-1 expression were observed. However, when the cultures were treated with IFN gamma, the EC acquired a fibroblast-like appearance, growth was disorg anized and PECAM-1 disappeared from cell junctions. The mean intensity expr ession and the percentage of EC expression of this antigen were analyzed by flow cytometry and significantly decreased after culture in the presence o f IFN gamma. The simultaneous addition of IFN gamma and IL-10 to the EC cul tures induced modifications similar to those observed in the presence of IF N gamma alone. Regulation of the expression of PECAM-1 with the subsequent functional implications seems to be dependent upon the IFN gamma signal and it is unaffected by IL-10. The different effects shown by IL-10 and IFN ga mma on the expression of PECAM-1 in EC could reflect opposite regulatory ac tions of the inflammatory response induced by these cytokines.