Review. Leukocyte and endothelial cell adhesion molecules in inflammation focusing on inflammatory heart disease

Abstract

In multicellular organisms the development of adhesion bonds, either among cells or among cells and components of the extracellular matrix, is a crucial process. These interactions are mediated by molecules which are named adhesion molecules and play a main role both at the early stages of the development of tissue integrity and later. Cell adhesion molecules (CAMs) have a key role in several pathologies such as cancer and inflammatory diseases. Selectins, integrins and immunoglobulin gene superfamily of adhesion receptors mediate different steps of leukocyte migration from the bloodstream towards the inflammatory foci. Leukocyte interactions with the vascular endothelium are highly orchestrated processes that include the capture of free-flowing leukocytes from the blood with subsequent leukocyte rolling, arrest, firm adhesion and ensuing diapedesis. These interactions occur under high shear stresses within venules and depend on multiple families of adhesion molecules. As a response to infection mediators, leukocyte gathering is considered to be crucial for the adequate defence of the organism to any kind of injury or infection. Endothelial activation contributes significantly to the systemic inflammatory response to bacteraemia and increased expression. Release of soluble endothelial markers into the circulation has been demonstrated together with elevated plasma levels of CAMs and has been reported in bacteraemic patients. It has been proposed that infection of endothelial cells with Staphylococcus aureus, Streptococcus sanguis, or Staphylococcus epidermidis induces surface expression of ICAM-1 and VCAM-1 and monocyte adhesion. In general, leukocyte/endothelial cell interactions such as capture, rolling, and firm adhesion can no longer be viewed as occurring in discrete steps mediated by individual families of adhesion molecules but rather as a series of overlapping synergistic interactions among adhesion molecules resulting in an adhesion cascade. These cascades thereby direct leukocyte migration, which is essential for the generation of effective inflammatory responses and the development of rapid immune responses.