Migration of monocytes across endothelium and passage through extracellular matrix involve separate molecular domains of PECAM-1.

Abstract

SummaryDuring the inflammatory response, the adhesion molecule PECAM plays a crucial role in transendothehal migration, the passage of leukocytes across endothelium. We report here an additional role for PECAM in the subsequent migration of monocytes through the subendothelial extraceHular matrix. PECAM has six immunoglobulin (Ig) superfamily domains. Monoclonal antibodies whose epitopes map to domains 1 and/or 2 selectively block monocyte migration through the endothelial junction, whereas those that map to domain 6 block only the migration through the extracellular matrix, trapping the monocyte between the endothelium and its basal lamina. Therefore, transendothelial migration (diapedesis) and passage through extracellnlar matrix (interstitial migration) are distinct and separable phases of monocyte emigration. Furthermore, distinct and separate Ig domains of PECAM are involved in mediating these two steps.

Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1

“…Furthermore, in agreement with previous findings, 15,22 PECAM-1 Ϫ/Ϫ mice exhibited a defect in neutrophil emigration through the vascular BM. Some previous studies have observed a role for PE-CAM-1 in migration through the endothelium as opposed to the BM, 44,45 but this was only seen when antibodies against specific domains of PECAM-1 were used, as opposed to full genetic deletion of the protein as with this work. Collectively, the present findings provide the first evidence to demonstrate that the adhesion molecules ICAM-2, JAM-A, and PECAM-1 can act in sequence to mediate distinct but sequential steps in supporting neutrophil emigration from the vascular lumen to the extravascular tissue ( Figure 6B).…”

Expression of platelet-endothelial cell adhesion molecule-1 (PECAM) by macaque trophoblast cells during invasion of the spiral arteries

“…In addition, circulating antibodies to PECAM prevented emigration of leukocytes in vivo following an inflammation stimulus (Bogen et al, 1994). Continued leukocyte migration through sub-endothelial extracellular matrix also involves PECAM, utilizing a separate heterophilic binding domain distinct from that used to traverse endothelial cells (Liao et al, 1995).…”

Endothelial cell functions

“…Another molecule expressed at the borders between confluent endothelial cells and on the surface of most leukocytes, CD99, could also be involved (Schenkel et al, 2002). PECAM seems also to be involved in the subsequent diapedesis across the subendothelial environment but requiring heterophilic binding to an unidentified ligand (Liao et al, 1995). In addition, release of neutrophil-derived proteases is also needed for this latest step (Duncan et al, 1999).…”