In inflammation, what is responsible for the early rolling of neutrophils (white blood cells) on the endothelium (inner lining of blood vessels)?

Selectins Mediate Early Neutrophil Rolling in Inflammation

In inflammation, the early "rolling" of neutrophils on endothelium is a function of selectins (answer A). This initial adhesive interaction is critical for the subsequent steps of neutrophil extravasation during the inflammatory response.

Mechanism of Neutrophil Rolling

The process of neutrophil migration from the bloodstream to sites of inflammation follows a well-defined sequence:

1. Initial Rolling (Selectin-Mediated)

   • P-selectin and E-selectin on activated endothelium interact with carbohydrate ligands on neutrophils 1, 2
   • L-selectin on neutrophils interacts with endothelial cell surface molecules 2
   • These selectin interactions create weak bonds that allow neutrophils to "roll" along the endothelial surface 3

2. Firm Adhesion (Integrin-Mediated)

   • After rolling, neutrophils become activated by chemotactic factors
   • This leads to upregulation of β2-integrins (CD11/CD18, including LFA-1 and Mac-1)
   • Integrins bind to ICAM-1 on endothelium, creating firm adhesion 2, 4

3. Transmigration

   • Neutrophils then migrate through the endothelial barrier into tissues
   • This process involves both integrin-dependent and independent mechanisms 5

Evidence Supporting Selectins in Rolling

The guideline evidence clearly identifies that P-selectin and E-selectin are expressed on the endothelial surface during inflammation 1. Figure 4 in the sepsis guideline specifically shows P-selectin and E-selectin on the endothelial surface during inflammatory responses 1.

Research studies provide direct evidence that:

• "Each member of the selectin family of adhesion molecules has been shown to support neutrophil rolling under conditions of flow" 2
• "Isolated human neutrophils adhered to E-selectin expressing L-cell monolayers... 47.8 ± 6.0% of these adherent cells were rolling" 3
• "Based on monoclonal antibody studies, P-selectin was required for normal PMNL migration to the joints" 5

Role of Other Adhesion Molecules

The other options function differently in the neutrophil adhesion cascade:

• Integrins (Option D): Mediate firm adhesion after rolling has occurred, not the initial rolling phase 2, 4
• Immunoglobulin Superfamily (Option C): Includes ICAM-1, which serves as a ligand for integrins during firm adhesion, not rolling 1, 4
• N-Cadherins (Option B): Not prominently mentioned in the inflammatory adhesion cascade; VE-cadherin is mentioned as an endothelial junction protein 1

Clinical Significance

Understanding this cascade is important because:

• Selectin-mediated rolling is the first step in neutrophil recruitment to inflammatory sites
• Targeting selectins has been investigated as a potential therapeutic approach for inflammatory conditions 6
• Dysfunction in this process can lead to abnormal inflammatory responses and tissue damage

The evidence clearly demonstrates that selectins are the primary mediators of the early rolling phase of neutrophil adhesion to endothelium during inflammation, making option A the correct answer.