Acute inflammation ensues with two phases of inflammation:
1. The vascular stage of inflammation consists of vasodilation and increased vascular permeability.
2. The cellular stage of inflammation involves the migration of leukocytes, predominantly neutrophils, into the affected tissues.
It is imperative that the body regulate the migration of the neutrophils, as this migration requires a series of sequential steps: rolling, integrin activation, firm attachment, transmigration, and chemotaxis.
Circulating neutrophils come in contact with the blood vessel wall via loose interactions between selectinreceptors on endothelial cells and glycoproteins on the neutrophil. The force of the blood flow breaks the bond just as another forms a little further down the endothelium. The neutrophils form, break, and form new bonds with the selectin receptors, it appears to roll along the endothelial surface.
As neutrophils roll along the endothelium, they contact the proinflammatory chemokine called IL-8, which is expressed by endothelial cells during times of inflammation. IL-8 binds to chemokine receptors on neutrophils triggering an intercellular cascade within the neutrophil. Thus the integrin receptor on the surface of the neutrophil is activated.
The activated integrin receptors on neutrophils bind strongly to intercellular adhesion molecules (ICAM) on the endothelial surface. This interaction is stronger than the force of blood flow, and the neutrophil stops rolling and adheres to the endothelial wall.
Once adhered, the neutrophil crawls to the closest endothelial cell border. The neutrophil cytoskeleton reorganizes, dramatically changing shape. A leading edge of the neutrophil inserts itself between two endothelial cells, allowing it to exit the circulation and enter the underlying connective tissue. This process is referred to as transmigration.
Once the neutrophil enters the affected tissue, it follows a gradient of chemokines, molecules from damaged cells and microbial products to the site of inflammation.