leukocyte extravasation
Summary
Leukocyte extravasation is the process by which white blood cells exit the bloodstream and migrate into tissue in response to infection or injury. It involves a sequential cascade: rolling, activation, firm adhesion, and transmigration. This process is essential for the inflammatory response and immune surveillance.
Detail
Leukocyte extravasation (also called diapedesis) is the multistep process allowing leukocytes to move from the blood vessel lumen into surrounding tissue at sites of inflammation or infection. The classic sequence includes: 1) Rolling - selectins (E-selectin and P-selectin on endothelium, L-selectin on leukocytes) mediate weak, transient adhesion causing leukocytes to roll along the endothelial surface, upregulated by histamine and TNF. 2) Activation/Tight adhesion - chemokines (e.g., IL-8) activate leukocyte integrins (LFA-1, Mac-1), which bind firmly to ICAM-1 and VCAM-1 on endothelium, causing the leukocyte to stop rolling. 3) Transmigration (diapedesis) - leukocytes squeeze between endothelial cells, a process mediated by PECAM-1 (CD31), to enter the interstitial tissue. 4) Chemotaxis - leukocytes migrate toward the site of injury/infection along a chemotactic gradient (e.g., bacterial products, complement C5a, leukotriene B4, chemokines). Clinical significance: Genetic defects in this pathway cause Leukocyte Adhesion Deficiency (LAD). LAD type 1 results from defective CD18 (integrin beta-2 subunit), causing recurrent bacterial infections, delayed umbilical cord separation, absent pus formation, and elevated neutrophil counts in blood (since they cannot leave the vasculature). LAD type 2 results from defective fucosylation affecting selectin ligands (Sialyl-Lewis X). Corticosteroids inhibit this process by decreasing integrin/selectin expression, contributing to neutrophilia and immunosuppression. This concept is frequently tested in relation to immunodeficiency disorders and the pharmacologic effects of glucocorticoids.
Sources
- Robbins and Cotran Pathologic Basis of Disease
- First Aid for the USMLE Step 1
- Kumar, Abbas, Aster - Robbins Basic Pathology
- Janeway's Immunobiology
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