The inflammatory response involves sequential adhesive interactions between cell adhesion molecules of leukocytes and the endothelium. Unlike the several adhesive steps that precede it, transendothelial migration (diapedesis), the step in which leukocytes migrate between apposed endothelial cells, appears to involve primarily one adhesion molecule, platelet–endothelial cell adhesion molecule (PECAM, CD31). Therefore, we have focused on PECAM as a target for antiinflammatory therapy. We demonstrate that soluble chimeras made of the entire extracellular portion of PECAM, or of only the first immunoglobulin domain of PECAM, fused to the Fc portion of IgG, block diapedesis in vitro and in vivo. Furthermore, the truncated form of the PECAM-IgG chimera does not bind stably to its cellular ligand. This raises the possibility of selective anti-PECAM therapies that would not have the untoward opsonic or cell-activating properties of antibodies directed against PECAM.

Despite the fact that VE-cadherin is a "nonclassical" cadherin by structure, it functions as a classic cadherin by imparting to cells the ability to adhere in a calcium-dependent, homophilic manner. On HUVEC it appears to play a role in maintaining monolayer integrity.

We have studied the expression of two of the receptors for fibroblast growth factors, FGFR-1 and FGFR-2, in response to ligand binding and in embryonal carcinoma (EC cells). Exposure of mouse fibroblasts to FGF-4 or FGF-2 results in a drastic downregulation of the mRNA levels for FGFR-2, while expression of FGFR-1 mRNA appears unaffected. Furthermore, FGF-4 transformed cells display low levels of FGFR-2 mRNA and these levels are significantly increased by treatment with anti FGF-4 neutralizing antibodies. In undifferentiated F9 EC cells, the levels of FGFR-2 mRNA are very low and increase substantially upon induction of differentiation. The levels of mRNA for FGFR-1 are again unaffected. To gain information on the regulation of expression of the gene encoding FGFR-2 (bek) we have cloned the FGFR-2 promoter region and used it to drive the expression of plasmids encoding the bacterial CAT enzyme. Transfection of these plasmids into FGF treated and untreated cells did not produce significant variation in CAT activity, suggesting that FGFR-2 downregulation in response to ligand binding occurs mainly by a post-transcriptional mechanism. In contrast, plasmids containing as little as 140 nt of the FGFR-2 promoter region were regulated in F9 cells, showing substantially higher expression in differentiated than in undifferentiated cells. It appears therefore that FGFR-2 expression in fibroblasts and EC cells is regulated by somewhat different mechanisms. In contrast, FGFR-1 expression does not vary substantially under the conditions shown to affect FGFR-2 expression. The implications of these findings are discussed.