Leukocyte migration into inflamed tissues

Leukocyte migration through activated venular walls is a fundamental immune response that is prerequisite to the entry of effector cells such as neutrophils, monocytes, and effector T cells to sites of infection, injury, and stress within the interstitium. Stimulation of leukocytes is instrumental in this process with enhanced temporally controlled leukocyte adhesiveness and shape-changes promoting leukocyte attachment to the inner wall of blood vessels under hydrodynamic forces. This initiates polarized motility of leukocytes within and through venular walls and transient barrier disruption facilitated sequentially by stimulated vascular cells, i.e., endothelial cells and their associated pericytes. Perivascular cells such as macrophages and mast cells that act as tissue inflammatory sentinels can also directly and indirectly regulate the exit of leukocytes from the vascular lumen. In this review, we discuss current knowledge and open questions regarding the mechanisms involved in the interactions of different effector leukocytes with peripheral vessels in extralymphoid organs.