ABSTRACT
Adhesion molecules belong to central regulators of leukocyte functions mediating cell-cell and cell-matrix interactions. In leukocytes, adhesion molecules mediate canonical functions participating in surface binding, transendothelial and interstitial migration. Additionally, each leukocyte type constitutively expresses or gains the expression of adhesion molecules characteristic for its functions. Th e eff ect on cell function depends on the type of adhesion molecule involved, the receptor partner it mobilizes, and the pathway of intracellular transduction it activates. Neutrophils and eosinophils have a limited panel of adhesion molecules which helps their rapid mobilization to the site of infectious or allergenic entrance, phagocytosis and degranulation. In monocytes, adhesion molecules facilitate phagocytosis and interstitial migration and support the broad diff erentiation capacity forming the subset of macrophages required in a particular tissue environment. Adhesion molecules on lymphocytes are key regulators of T and B cell maturation, tissue-specifi c traffi cking and antigen presentation. Th e major groups of adhesion molecules identifi ed in leukocytes include selectins together with their ligands mucins, and integrins with their specifi c ligands. Ligation of integrins by their counterparts or by the proteins of extracellular matrix containing RGD-motif induces conformation changes and clustering of integrins in cell membrane followed by intracellular signals (outside-in signaling). Stimulation of leukocytes through growth factor receptors, G-protein coupled receptors, and immunoreceptors potentiates the affi nity of adhesion molecules and their reactivity (inside-out signaling). A net of intracellular signaling initiated by these receptors
is mediated by a combination of adaptor molecules specifi c for each receptor followed by activation of PI3-kinase or protein tyrosine kinases. Coordination of inside and outside integrin signaling is proved to be crucial in the pathogenesis of acute and chronic infl ammatory and metabolic conditions including sepsis, atherosclerosis, rheumatoid arthritis, multiple sclerosis and diabetes mellitus. Treatment modalities targeting adhesion molecules are on the way to becoming clinical reality.
