Leukocyte diapedesis, chemotaxis, and early inflammatory infiltrates
THE CONTEXT
After adhering to endothelium, leukocytes cross the vessel wall and follow chemical gradients toward injury. The predominant recruited cell changes with time.
Crossing the vessel wall
•
Transmigration, also called diapedesis, is leukocyte extravasation through the vessel wall, primarily by squeezing between endothelial junctions.
•
Platelet endothelial cell adhesion molecule-1 (PECAM-1), also called CD31, is expressed on leukocytes and endothelial cells and mediates binding events required for endothelial traversal.
•
After crossing endothelium, leukocytes pierce the basement membrane, probably by secreting collagenases, and enter extravascular tissue.
•
Locally produced chemokines establish diffusion gradients that direct leukocyte movement through tissues.
Chemotactic signals and movement
•
Chemotaxis is locomotion along a chemical gradient toward the site of injury.
•
Potent chemoattractants include bacterial products, particularly peptides with N-formylmethionine termini; chemokines; complement components, particularly C5a; and leukotrienes.
•
These chemoattractants are produced during infections, tissue damage, and immunologic reactions and bind G protein-coupled receptors on leukocytes.
•
Receptor signaling activates second messengers that induce actin polymerization at the leading edge and localization of myosin filaments at the back of the cell.
•
Leukocytes extend filopodia that pull the cell in the direction of extension, producing migration toward locally generated chemoattractants.
Typical timing of cellular recruitment
•
The inflammatory infiltrate varies with the age of the response and the type of stimulus.
•
In most acute inflammatory reactions, neutrophils predominate during the first 6–24 hours and are replaced by monocytes within 24–48 hours.