Integrins in bacterial pathogenesis and inflammatory disease: An overview of current perspective

Cell adhesion molecules (CAMs) have been recognized to play a major role in a variety of physiological and pathological phenomena like specificity of cell-cell binding and the interactions between cells and extracellular matrix proteins, Some of them may also function as receptors that trigger intracellular pathways and participate in cellular processes such as migration, proliferation, differentiation, and cell death. The receptors that mediate adhesion between epithelial cells, which are discussed in this review, include integrins, selectins, the immunoglobulin superfamily members and cadherins. Several of these molecules are exploited by bacterial pathogens to establish tight contact with eukaryotic cells. Using the example of integrins, cadherins and IgCAMs, this review illustrates the signaling capacity of cell adhesion receptors and highlights a number of bacterial adhesins that are known to engage these receptors. The role of the receptor-adhesin interaction in the course of the infection is discussed. Integrin CAMs that mediate leukocyte migration are therapeutic targets for the treatment of inflammatory disease. Antibody blockade of the β 7 integrins, α 4 β 7 and α E β 7 and the vascular ligand MAdCAM-1 prevents the development of the multiple sclerosis-like disease experimental autoimmune encephalomyelitis (EAE). The combination of CAM-based therapy with treatments that restore the functions of affected organs represents a promising therapeutic approach. Cell adhesion molecules including β 7 molecules, MAdCAM-1, VCAM1 and ICAM-1 expressed on dendritic cells, act both as receptors for natural killer (NK) cells, and as costimulators of T cell proliferation. Their introduction into tumours in situ induces potent systemic immunity. A remarkable synergies by combining CAM-based cancer immunotherapy with anti-angiogenic agents (DMXAA, anti-HIF-1α, and angiostatin) starve tumours of blood supply or target molecules that allow tumour cells to evade programmed cell death.