U01.04.015 Leukocyte extravasation

Leukocyte extravasation is a critical process where white blood cells (WBCs) move out of the circulatory system toward the site of tissue injury or infection. This process predominantly occurs at postcapillary venules.

Steps in Leukocyte Extravasation

Margination and Rolling
- Vasculature/Stroma: E-selectin (upregulated by TNF and IL-1), P-selectin (released from Weibel-Palade bodies), GlyCAM-1, CD34
- Leukocyte: Sialyl LewisX, L-selectin
- Clinical Note: This step is defective in leukocyte adhesion deficiency type 2 (LAD-2), which involves a deficiency in Sialyl LewisX.
Tight Binding (Adhesion)
- Vasculature/Stroma: ICAM-1 (CD54), VCAM-1 (CD106)
- Leukocyte: CD11/18 integrins (LFA-1, Mac-1), VLA-4 integrin
- Clinical Note: This step is defective in leukocyte adhesion deficiency type 1 (LAD-1), involving a deficiency in the CD18 integrin subunit.
Diapedesis (Transmigration)
- Vasculature/Stroma: PECAM-1 (CD31)
- Leukocyte: PECAM-1 (CD31)
- Description: WBCs travel between endothelial cells and exit the blood vessel.
Migration
- Vasculature/Stroma: Chemotactic factors such as C5a, IL‑8, LTB4, kallikrein, and platelet-activating factor.
- Leukocyte: Various receptors respond to chemotactic signals.
- Description: WBCs travel through the interstitium to the site of injury or infection.

Table: Key Molecules Involved in Leukocyte Extravasation

Step	Vasculature/Stroma Molecules	Leukocyte Molecules	Clinical Notes
Margination and Rolling	E-selectin, P-selectin, GlyCAM-1, CD34	Sialyl LewisX, L-selectin	Defective in LAD-2 (Sialyl LewisX deficiency)
Tight Binding (Adhesion)	ICAM-1 (CD54), VCAM-1 (CD106)	CD11/18 integrins (LFA-1, Mac-1), VLA-4 integrin	Defective in LAD-1 (CD18 integrin subunit deficiency)
Diapedesis	PECAM-1 (CD31)	PECAM-1 (CD31)	WBC exits the blood vessel through endothelial gaps
Migration	Chemotactic factors (C5a, IL-8, LTB4, etc.)	Various receptors	WBC migrates towards the site of injury or infection

Table: Key Molecules Involved in Leukocyte Extravasation

Points to Remember:

Margination and rolling occur through the interaction of selectins and Sialyl LewisX on leukocytes.
Tight binding (adhesion) is critical for leukocytes to firmly attach to the endothelium, primarily mediated by integrins.
Diapedesis (transmigration) allows leukocytes to exit the bloodstream, guided by PECAM-1 interactions.
Migration is driven by chemotactic signals that direct leukocytes to the site of infection or injury.
Deficiencies in adhesion molecules like Sialyl LewisX or CD18 integrins can lead to immunodeficiency disorders such as LAD-2 and LAD-1.

USMLE Step 1 Review Series

Curriculum

U01.04.015 Leukocyte extravasation

Steps in Leukocyte Extravasation

Table: Key Molecules Involved in Leukocyte Extravasation

Points to Remember:

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