cell injury

• The components of cellular event inflammation includes understanding of the influx of leukocytes that is neutrophils and monocytes to the site of injury
• Leukocyte migration from lumen to site of injury

  1. Margination

  2. Rolling

  3. Adhesion

  4. Transmigration

  5. Chemotaxis
• Margination


  Redistribution of leukocytes along the margins of the blood vessels
• Rolling


  Transient binding and detachment of leukocytes to endothelial cells
• Selectins


  • Family of proteins that mediate the rolling phenomenon
  • P-selectin and E-selectin are expressed on activated endothelial cells
  • L-selectin is expressed on leukocytes
• Adhesion


  Firm binding of leukocytes to endothelial cells mediated by integrins
• Integrins


  • Transmembrane glycoproteins involved in adhesion
  • Expressed on activated leukocytes
  • Bind to ligands on endothelial cells
• Transmigration


  Passage of leukocytes through the endothelial cell layer
• PECAM-1


  • Cellular adhesion molecule that mediates transmigration
  • Also known as CD31
• Chemotaxis


  Migration of leukocytes towards a chemotactic gradient
• Chemotactic factors


  • Exogenous (bacterial products)
  • Endogenous (cytokines, complement factors, arachidonic acid metabolites)
• Neutrophils predominate in the initial stages of acute inflammation, followed by monocytes after 24-48 hours
• Neutrophils are more numerous, respond more rapidly to chemokines, and adhere more firmly to adhesion molecules compared to other leukocytes
• Neutrophils are short-lived and undergo apoptosis, while monocytes survive longer and proliferate in tissues to become macrophages
• There are exceptions, such as Pseudomonas infection where neutrophils continue to be recruited for several days, and viral infections where lymphocytes predominate
• Understanding the mechanism of leukocyte recruitment provides potential therapeutic targets for controlling harmful inflammation
• Examples of therapeutic targets include TNF blockers and integrin antagonists