42 2.4: Extravasation of Leukocytes

How Leukocytes Travel From Circulation to Tissues

 

Definitions

Extravasation– In inflammation, is the process of the recruitment of white blood cells (leukocytes) from blood vessels into inflamed o damaged tissue to create an immune response. Also known as diapedesis

 

 

Leukocyte recruitment to inflamed tissues begins the immune response. Generally, this process can be divided into 6 steps (Vestweber 692) :

  1. Capture- Selectins ( P/E-selectins) on the endothelium of tissues slow down leukocytes in the bloodstream
  2. Rolling- Movement on the vascular wall leads to pulling of the membrane tethers, which wrap around the leukocytes to secure them to the endothelium. This depends on many different extracellular signalling factors.
  3. Activation- Leukocytes are activated by signals ( chemokines and cytokines such as C5a) on the endothelium.
  4. Adhesion- ICAM1 and VCAM1 on the endothelial membrane bind to integrins on the leukocytes, creating adhesion of the leukocyte to the endothelial membrane
  5. Diapedesis- The leukocyte enters through the endothelium into underlying tissue which is triggered by leukocyte signalling and endothelial cell adhesion molecules such as PECAM1, JAMS, ESAM, CD99, and PVR. This process depends on the opening of endothelial cell junctions dependent on VE-cadherin.
  6. Migration- The leukocyte can then travel within the inflamed tissue to where an immune response is required.
Figure 9: Visualization of leukocyte extravasation including three cadherins, integrins, proteins, and receptors involved. Figure from: Vestweber, D. How leukocytes cross the vascular endothelium. Nat Rev Immunol 15, 692–704 (2015). https://doi.org/10.1038/nri3908

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Selected Topics in Health and Disease (Vol. 3) Copyright © 2020 by Class of HMB422 2020 and Dr. William Ju. All Rights Reserved.

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