Integrins of Macrophages and Macrophage-Like Cells

The integrins are a family of heterodimeric adhesion receptors present on virtually every cell in metazoan organisms. Macrophage integrins are involved in adhesion to extracellular matrix and to other cells, in phagocytosis, and in cell migration and spreading. Macrophage integrins also transduce signals from the extracellular environment, both through activation of specific kinase cascades and through modulation of cytoskeletal elements. The ligand-binding ability of macrophage integrins can be regulated by environmental cues including growth factors, lipid mediators, bacterial peptides, and fragments of complement, clotting, and other proteins that may accumulate at sites of inflammation. In addition, integrins can function as components of multimolecular plasma membrane complexes that include tetraspanins, proteases, and other receptors. These multimolecular complexes can be endowed with functional properties not inherent in the isolated components. This review summarizes current understanding of the complex biology of macrophage integrins. The involvement of integrins in many macrophage processes fundamental to the function of these cells for inflammation and host defense makes them double-edged swords as candidates for therapeutic intervention. Beneficial effects of broad integrin blockade in ameliorating idiopathic inflammation may be accompanied by unacceptable susceptibility to infection or other deleterious side effects. However, more specific blockade of less widely expressed integrins holds the promise of a better therapeutic effect. For example, recent studies in animals suggest potential therapeutic use for blockade of osteoclast αVβ3 in osteoporosis and of T-cell and monocyte α1β1 and α2β1 in arthritis. Further understanding of the molecular mechanisms through which macrophage integrins control key events in a variety of diseases may lead to the development of inhibitors of even greater specificity. The integrins remain appealing therapeutic targets because of their central role in macrophage biology.