A10-year-old male child complains of pain and swelling in the left foot. He gives a history of injury while playing. Migration of leukocytes to the site of injury is mediated by
LEUKOCYTE RECRUITMENT
• The journey of leukocytes from the vessel lumen to the tissue is a multistep process that is mediated and controlled by adhesion molecules and cytokines called chemokines
LEUKOCYTE ADHESION
• Extravasation is the sequence of events in the journey of leukocytes from vessel lumen to interstitial tissue which include the following steps
> Margination - leukocytes assume a peripheral portion of lumen along endothelial surface
> Rolling - leukocytes adhere transiently, detach and bind again and finally adhere firmly
> Rolling is mediated by Selectins (P, L and E-selectins)
> Firm adhesion is mediated by Integrins (LFA-1. MAC-1, VLA-4, α4β7)
> Pavement - endothelium virtually lined by leukocytes
LEUKOCYTE MIGRATION
• Diapedesis or transmigration
> Leukocyte migration through endothelium
> Occurs mainly in post capillary venules
> Adhesion molecules involved - CD31 or PECAM-1 (platelet endothelial cell adhesion molecule)
CHEMOTAXIS
• Leukocyte migration toward the site of injury
• Locomotion oriented along a chemical gradient
• Chemo-attractants
> Exogenous - bacterial products (most common)
> Endogenous
■ Cytokines, particularly - IL-8
■ Complement, particularly - C5a
■ Arachidonic acid metabolites particularly - LTB4
• Neutrophils predominate in the inflammatory infiltrate during the first 6 to 24 hours
• Neutrophils are replaced by monocytes in 24 to 48 hours
• In Pseudomonas infection - cellular infiltrate is dominated by neutrophils for several days
• In viral infections, lymphocytes may be the first cells to arrive
Cytokines
Histamine
Chemokines
Prostaglandins