Selectins and Leukocyte Rolling: The Adhesion Cascade

Selectins are cell adhesion molecules that bind carbohydrates (sialylated sugar groups on glycoproteins) and mediate the first, weak, transient contact between a leukocyte and the blood vessel wall. That contact makes the leukocyte roll along the endothelium instead of being swept past.

The four-step cascade

1. Rolling (selectins). Inflamed endothelium displays selectins (P-selectin and E-selectin). They bind carbohydrate ligands on the leukocyte. The bonds form and break quickly, so the cell slows and rolls.
2. Activation (chemokines). Chemokines on the endothelial surface bind receptors on the rolling leukocyte and switch on its integrins.
3. Firm adhesion (integrins). Activated integrins on the leukocyte bind ICAMs (immunoglobulin superfamily proteins) on the endothelium. The cell stops.
4. Transmigration (diapedesis). The leukocyte squeezes between endothelial cells and follows the chemical gradient into the tissue.

The order to remember is selectin, then integrin: selectins slow the cell, integrins stop it.

Three selectins

Selectin binding needs calcium, like cadherins.

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Why the bond has to be weak

Selectin-carbohydrate bonds are low affinity and short lived. That is what lets the leukocyte keep moving and roll. If selectins held tightly, the cell would stick at the first spot it touched. Firm adhesion is the job of integrins and ICAMs after activation.

What goes wrong

In leukocyte adhesion deficiency, integrin function is lost, so leukocytes roll but cannot adhere firmly or leave the blood. Blood leukocyte counts are high while infections at tissue sites go unchecked.

Common traps

• Swapping selectins and integrins. Selectins roll; integrins grip.
• Saying selectins bind proteins. They bind carbohydrates.
• Forgetting the signal. Chemokines activate integrins between rolling and firm adhesion.
• Calling ICAMs integrins. ICAMs are on the endothelium; integrins are on the leukocyte.

One-minute recap

• Selectin: carbohydrate binding, weak, rolling.
• Chemokine signal activates integrins.
• Integrin + ICAM: firm adhesion, then diapedesis.