Soluble Domain 1 of Platelet–Endothelial Cell Adhesion Molecule (PECAM) Is Sufficient to Block Transendothelial Migration In Vitro and In Vivo

Abstract

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.

CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

“…Our static assay, which employs HUVEC plated atop collagen gels set in 96-well plates (25), allows the EC to form a physiologic basal lamina and physiological matrix into which they can migrate. Findings from this assay have all been verified in vivo (34,35). The diapedesis step, unlike earlier steps of rolling and adhesion, occurs largely independently of shear (36,37).…”

The Junctional Adhesion Molecule-C Promotes Neutrophil Transendothelial Migration in Vitro and in Vivo

“…Previously, JAM-A was shown to participate in this process both by undergoing a homophilic interaction and by binding to LFA-1 (15,16). Moreover, PECAM-1 that is expressed diffusely on the surfaces of most leukocytes and is concentrated at interendothelial borders (39) has been implicated as a critical mediator of transendothelial migration (8,11). Recently, PECAM-1 was found to recycle along interendothelial borders into segments of the junction, across which leukocytes are actively migrating (10).…”

Induction of Hyporesponsiveness and Impaired T Lymphocyte Activation by the CD31 Receptor:Ligand Pathway in T Cells

“…CD31 has been demonstrated to play a role in the transmigration of PMN, monocytes, and NK cells in both in vitro and in vivo models (15,22). Recent evidence coming from experiments using CD31 Ϫ mice and mice transgenic for a soluble CD31-receptorglobulin (CD31Rg) confirm the involvement of CD31 in the recruitment of leukocytes to inflammatory sites (23,24).…”