Adhesion mechanisms regulating the migration of monocytes

Key Points Monocytes are progenitors of both tissue macrophage and dendritic-cell subsets. Two classes of circulating monocytes have been identified; these have different migration properties and chemokine-receptor expression patterns. The trafficking of monocytes into tissues requires the orchestrated activation of integrins by specific chemokines. Signal transduction induced by chemokines targets cytosolic integrin-activating proteins, such as RHOA, RAP1, talin or PYK2, which results in cell adhesion to the blood-vessel wall. Transendothelial migration of adherent monocytes requires polarization of the adherent monocytes and remodelling of the endothelial-cell junctions. The trafficking of monocytes to their final tissue depends on chemotactic gradients and specific expression of adhesion molecules, which are regulated by inflammation. Because of their phagocytic activity and their ability to differentiate into antigen-presenting cells, monocytes participate in both innate and adaptive immune responses. They derive from bone-marrow progenitor cells, circulate in the blood as monocytes and differentiate into tissue macrophages or myeloid dendritic cells in the periphery. After activation by an antigenic challenge in the tissues, they can contribute to the local resolution of the injury or can migrate farther to secondary lymphoid organs. Recruitment of these cells from the blood to the tissue and from the tissue to the lymph nodes requires orchestrated adhesive interactions between leukocytes and the vascular or lymphatic endothelium. Here, we discuss the signals by which chemokines regulate the leukocyte-adhesion molecules that are essential for transendothelial migration, and we describe the routes taken by monocytes and myeloid dendritic cells to reach their final destination.