Interactions of migrating T lymphocytes, inflammatory mediators, and the extracellular matrix

Leukocytes are mobile units of the immune system. The process of leukocytes migration from blood vessels to inflamed tissues involves two major steps: (1) extravasation through the vessel wall and (2) movement through the underlying basement membrane and extracellular matrix (ECM). The ECM is a complex macromolecular mesh composed of proteoglycans and adhesive glycoproteins, such as collagen, laminin, and fibronectin, and serves as a supportive structure surrounding cells and can also provide co-stimulatory signals to immune cells. Hence, the basement membrane and the ECM play important roles as contexts in which biological processes take place, and therefore these moieties should be considered as microenvironment milieu in which extravasating cells function, communicate, and signal their messages; the outcome of which can result in the immunological eradication of hazardous elements. During migration, leukocytes continuously exchange information with the surrounding microenvironment. This cross-talk, which is also influenced by cytokines and chemokines, determines the type and the strength of the resulting immune response to foreign determinants. As suggested in the present article, these signals determine the response to a specific antigen and enable the migrating leukocytes to recognize any insult in their vicinity and to rapidly modify their activities.