Endothelial Cell Junctional Adhesion Molecules: Role and Regulation of Expression in Inflammation.

Endothelial cells line the lumen of all blood vessels and play a critical role in maintaining the barrier function of the vasculature. Sealing of the vessel wall between adjacent endothelial cells is facilitated by interactions involving junctionally expressed transmembrane proteins, including tight junctional molecules, such as members of the junctional adhesion molecule family, components of adherence junctions, such as VE-Cadherin, and other molecules, such as platelet endothelial cell adhesion molecule. Of importance, a growing body of evidence indicates that the expression of these molecules is regulated in a spatiotemporal manner during inflammation: responses that have significant implications for the barrier function of blood vessels against blood-borne macromolecules and transmigrating leukocytes. This review summarizes key aspects of our current understanding of the dynamics and mechanisms that regulate the expression of endothelial cells junctional molecules during inflammation and discusses the associated functional implications of such events in acute and chronic scenarios.

Function of junctional adhesion molecules (JAMs) in leukocyte migration and homeostasis.

Homeostasis is a word widely used in the scientific community to refer to the property of a system to maintain its uniformity and functionality. In living organisms, the word refers to the concept enunciated 150 years ago by C. Bernard by which external variations must be compensated for in order to maintain internal conditions compatible with life. This is especially true in the case of highly dynamic system such as the hematopoietic system that requires the coordinated control of cell proliferation and death within specialized microenvironments that are anatomically distinct. As a consequence, hematopoietic cell adhesion and migration must be tightly controlled in order for hematopoietic cells to reach and to be maintained in appropriate microenvironments. The junctional adhesion molecules (JAMs) are adhesion molecules that belong to the immunoglobulin superfamily (IgSf) and that have been initially identified as important players controlling vascular permeability and leukocyte transendothelial migration. This involves the regulated localization of the JAMs at lateral endothelial cell/cell borders and their interaction with leukocyte integrins. More recently, some of the JAM family members have also been found to be expressed by stromal cells and to regulate chemokine secretion within lymphoid organs, acting not only on leukocyte transendothelial migration, but also on hematopoietic cell retention within specialized microenvironments. This review summarizes recent progress in understanding the role of the JAMs in leukocyte adhesion and migration to tentatively draw an integrated view of the homeostatic function of the JAMs within the hematopoietic system.