Learning Objective:
Understand the stepwise process of leukocyte extravasation, the key adhesion molecules involved at each stage, and the associated leukocyte adhesion deficiencies.
Leukocyte extravasation is the process by which white blood cells (WBCs) exit the bloodstream and migrate to sites of tissue injury or infection. This process occurs predominantly at postcapillary venules and proceeds through four coordinated steps:
Activity
Margination and Rolling
Definition: Leukocytes move from the center of blood flow to the endothelial surface and roll along the vessel wall.
Key interactions:
- Endothelial selectins:
- E-selectin – upregulated by TNF-α and IL-1
- P-selectin – rapidly translocated to the endothelial surface via exocytosis from Weibel-Palade bodies
- Leukocyte ligands:
- Sialyl Lewisⁿ (Sialyl Lewis X) on leukocytes
- Other endothelial ligands: GlyCAM-1, CD34
- Leukocyte selectin: L-selectin
- Clinical correlation:
- Defective in Leukocyte Adhesion Deficiency (LAD) type 2 due to ↓ Sialyl Lewis X
Tight Binding (Firm Adhesion)
Definition: Leukocytes firmly adhere to the endothelium, stopping rolling.
Key interactions:
- Endothelial adhesion molecules:
- ICAM-1 (CD54)
- VCAM-1 (CD106)
- Leukocyte integrins:
- CD11/CD18 integrins (eg, LFA-1, Mac-1)
- VLA-4 integrin
- Clinical correlation:
- Defective in Leukocyte Adhesion Deficiency (LAD) type 1 due to ↓ the CD18 integrin subunit
Diapedesis (Transmigration)
Definition: Leukocytes migrate between endothelial cells to exit the blood vessel.
Key interactions:
- PECAM-1 (CD31) is expressed on both leukocytes and endothelial cells
Migration (Chemotaxis)
Definition: Leukocytes move through the interstitium toward the site of injury or infection.
Guided by chemotactic factors:
- C5a
- IL-8
- LTB₄
- 5-HETE
- Kallikrein
- Platelet-activating factor
- N-formylmethionyl peptides (bacterial products)
