INFLAMMATION Part 2: Cellular Events- Leukocyte Recruitment.

This section introduces cellular events in inflammation, specifically the recruitment of leukocytes to injury sites. Learning objectives include understanding leukocyte recruitment within the lumen, across the vessel wall, and outside in the tissue, as well as therapeutic implications. Leukocytes ingest and destroy foreign bodies through phagocytosis and secrete growth factors crucial for repair. This multi-step process is regulated by adhesion molecules and chemokines.

The leukocyte journey begins with margination, where leukocytes move to the periphery of blood vessels due to blood flow slowing down (stasis). This is followed by rolling, a transient binding and detachment from endothelial cells, mediated by selectins (P, E, and L selectins). Finally, firm adhesion occurs when integrins on leukocytes bind to integrin ligands (VCAM-1 and ICAM-1) on activated endothelial cells, under the influence of TNF and IL-1.

After firm adhesion, leukocytes squeeze between endothelial cells, a process called diapedesis or transmigration. This is facilitated by adhesion molecules like PECAM-1 (CD31), which are present on both leukocytes and endothelial cells. Once through, leukocytes secrete collagenases to break down the basement membrane and enter the extravascular space.

Chemotaxis is the migration of leukocytes towards a chemical gradient of chemoattractants. These can be exogenous (bacterial products) or endogenous (cytokines, complement products like C3a and C5a, or arachidonic acid metabolites like leukotriene B4). Chemoattractants bind to specific receptors on leukocytes, leading to actin polymerization and myosin localization, causing the leukocyte to extend pseudopods and move towards the source of the stimulus.

In acute inflammation, neutrophils typically predominate in the initial 6-24 hours due to their higher numbers, rapid response to chemokines, and firm attachment. Monocytes follow after 24-48 hours, surviving longer and becoming macrophages in tissues. Exceptions include Pseudomonas (prolonged neutrophil recruitment), viral infections (lymphocyte predominance), and allergic reactions (eosinophil predominance). Understanding these mechanisms helps in identifying therapeutic targets, such as TNF blockers and integrin antagonists, to control harmful inflammation.