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Leukocyte Extravasation

Overview

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Introduction

  • Leukocytes play an important role in eliminating offending agents
    • neutrophils and macrophages are capable of destroying microbes, necrotic tissue, and foreign substances
  • The process of leukocytes migrating from the blood vessel to tissue involves multiple steps and are mediated by adhesion molecules and chemokines
    • margination
      • leukocytes become redistributed closer to the vessel wall
    • rolling
      • leukocytes transiently attach to endothelium and then detach
        • these cells therefore “roll” on the vessel wall
      • the endothelium possesses E-selectin and P-selectin
        • cytokines from the inflamed tissue regulate selectin expression
        • Sialyl-Lewis X protein binds to E-selectin and P-selectin
          • found on leukocytes
    • firm endothelial adhesion
      • mediated by integrin proteins
        • vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule-1 (ICAM-1) are found on the endothelium
        • low affinity integrin are found on leukocytes
    • migration through the vessel wall
    • migration to tissue
StepMolecule on Vasculature/StromaMolecule on Leukocyte
1. Loose adhesion, rolling E-selection, P-selectinSialyl Lewis 
2. Tight adhesion ICAM-1LFA-1 (integrin)
3. Diapedesis PECAM-1PECAM-1
4. Migration through ECM Bacterial products, C5a, IL-8, LTB4, KallikreinVarious