α4-Integrin-dependent emigration of monocytes

The recent studies, reviewed here, illustrate that monocytes utilize both the CD11/ CD18 and α₄ (VLA-4; CD49d/CD29)adhesion molecule complexes in vivo to migrate to acute or chronic inflammatory reactions; that either of these integrin family members can mediate nearoptimal monocyte migration; and that both CD18 and VLA-4 need to be completely blocked to suppress monocyte infiltration into inflammation. The resultsof in vivo studies are in strong agreement with conclusions drawn from studies of human monocyte migration across vascular endothelium in vitro [15, 48].The picture that has emerged is not only that there is a major role for α₄ integrin in monocyte recruitment toinflammation, but also that integrin blocking therapeutic strategies to control monocyte-macrophage participation in immuno-inflammatory reactions mustbe designed to block the CD18 (β₂) and α₄(VLA-4) integrins simultaneously. Alternatively, their respective ligands, ICAM-1 (ICAM-2), and VCAM-1 (including both domain 1 and 4 of VCAM-1) on vascular endotheliumneed to be blocked. Ongoing studies in this area show great promise in transplantation, autoimmune and allergic disease models. It is very likely that the mechanismsoutlined above are also relevant to the process whereby monocytes adhere to and migrate across the endothelium in major arteries during the development of atherosclerosis[67]. Thus, the widespread implications of understanding the basic interactions governing monocyte migration will be a fruitful and important line of investigation.