Figure 1.

The multi-step leukocyte adhesion cascade: (1) Endothelial cells at a site of inflammation are activated by stromal derived inflammatory cytokines such as TNF-α, IL-1β and IFN-γ. Induction of transcriptional activity results in the expression of adhesion molecules and chemokines which coordinate leukocyte recruitment. (2) Leukocytes are recruited from flowing blood by specialised receptors of the selectin family and VCAM-1, which also support rolling adhesion. (3) Chemokine signals activate the β1 and β2 integrins on rolling leukocytes. (4) Adhesion is stabilised and the leukocytes become firmly adherent to the endothelial cell. (5) In response to additional signals, e.g. from PgD2, the leukocyte cytoskeleton undergoes remodelling driving shape change (spreading) and dynamic integrin-mediated migration. (6) Leukocytes migrate across and through the endothelial cell monolayer and onwards into tissue.