Selectins Mediate Early Neutrophil Rolling on Endothelium in Inflammation

The early "rolling" of neutrophils on endothelium during inflammation is primarily mediated by selectins (answer choice a).

Neutrophil Recruitment Cascade

Neutrophil recruitment to sites of inflammation follows a well-defined cascade that begins with the initial capture and rolling of neutrophils along the endothelial wall of blood vessels, which is mediated by selectins 1, 2
The activated endothelium expresses adhesion molecules such as P-selectin and E-selectin on its luminal surface, which interact with ligands on neutrophils, promoting this initial rolling phase 1
This selectin-mediated rolling is a prerequisite for subsequent firm adhesion and transmigration of neutrophils into inflamed tissues 3

There are three types of selectins involved in the inflammatory process: E-selectin, P-selectin, and L-selectin 2
E-selectin and P-selectin are expressed on activated endothelial cells, while L-selectin is constitutively expressed on neutrophils 2, 4
Studies have demonstrated considerable overlap in the functions of E- and P-selectin; loss of both selectins is required to significantly impair neutrophil accumulation in models of acute inflammation 2
L-selectin on flowing neutrophils can also interact with ligands on already adherent neutrophils, promoting continuous recruitment at sites of previous neutrophil accumulation 4

Selectins are a family of cell adhesion molecules that recognize carbohydrate ligands and mediate the initial tethering and rolling of leukocytes on the endothelium 1, 5
This selectin-mediated rolling allows neutrophils to sample inflammatory signals from the endothelium 3
The rolling velocity of neutrophils systematically decreases as a function of their contact time with the inflamed endothelium 3
If sufficient activation occurs during rolling, β2 integrins on neutrophils switch to a high-affinity conformation, leading to firm adhesion 3

While selectins mediate the initial rolling phase, the firm adhesion of neutrophils to the endothelial surface is mediated by the interaction between leukocyte integrins (such as LFA-1) and endothelial adhesion molecules ICAM-1 and VCAM-1 1
N-cadherins are not significantly involved in neutrophil-endothelial interactions during inflammation 1
The immunoglobulin superfamily members (including ICAM-1 and VCAM-1) are primarily involved in the later transmigration phase of neutrophil recruitment, not the initial rolling 1
Complement activation may enhance neutrophil recruitment but is not directly responsible for the early rolling phenomenon 6

Understanding the molecular mechanisms of neutrophil rolling has important clinical implications, as excessive neutrophil recruitment contributes to tissue injury and organ dysfunction in pathological conditions 1
Volatile anesthetics like isoflurane and sevoflurane have been shown to impair neutrophil adhesion to human endothelial cells, which may provide beneficial effects in ischemic settings 6, 7
These anesthetics bind to lymphocyte function-associated antigen-1 (LFA-1), blocking its interaction with ICAM-1 and inhibiting immune cell adhesion 7
Targeting selectin-mediated rolling could potentially modulate inflammatory responses in various clinical conditions 8