Selectins Rolling Leukocytes and the Inflammatory Response

Human bodies are constantly exposed to a plethora of bacteria, viruses, and other inflammatory substances. To combat these infectious and toxic agents, the body has developed a carefully regulated inflammatory response system. Part of that response is the orderly migration of leukocytes to sites of inflammation. Leukocytes literally roll along the vascular wall and into the tissue site of inflammation. This rolling movement is mediated by reversible adhesive interactions between the leukocytes and the vascular surface.

These interactions involve adhesion proteins called selectins, which are found both on the rolling leukocytes and on the endothelial cells of the vascular walls. Selectins have a characteristic domain structure, consisting of an N-terminal extracellular lectin domain, a single epidermal growth factor (EGR) domain, a series of two to nine short consensus repeat (SCR) domains, a single transmembrane segment, and a short cytoplasmic domain. Lectin domains, first characterized in plants, bind carbohydrates

L-Selectin

Selectin receptors

Leukocyte

Selectin receptor

L-Selectin

Selectin receptors

Leukocyte

Selectin receptor

Selectin Endothelial Cell

E-Selectin Endothelial cell

P-Selectin

A diagram showing the interactions of selectins with their receptors.

E-Selectin Endothelial cell

P-Selectin

A diagram showing the interactions of selectins with their receptors.

with high affinity and specificity. Selectins of three types are known—E-selectins, L-selectins, and P-selectins. L-selectin is found on the surfaces of leukocytes, including neutrophils and lymphocytes, and binds to carbohydrate ligands on endothelial cells. The presence of L-selectin is a necessary component of leukocyte rolling. P-selectin and E-selectin are located on the vascular endothelium and bind with carbohydrate ligands on leukocytes. Typical neutrophil cells possess 10,000 to 20,000 P-selectin binding sites. Selectins are expressed on the surfaces of their respective cells by exposure to inflammatory signal molecules, such as histamine, hydrogen peroxide, and bacterial endotoxins. P-selectins, for example, are stored in intracellular granules and are transported to the cell membrane within seconds to minutes of exposure to a triggering agent.

Substantial evidence supports the hypothesis that selectin-carbohydrate ligand interactions modulate the rolling of leukocytes along the vascular wall. Studies with L-selectin-deficient and P-selectin-deficient leukocytes show that L-selectins mediate weaker adherence of the leukocyte to the vascular wall and promote faster rolling along the wall. P-selectins conversely promote stronger adherence and slower rolling. Thus, leukocyte rolling velocity in the inflammatory response could be modulated by variable exposure of P-selectins and L-selectins at the surfaces of endothelial cells and leukocytes, respectively.

SCR repeat

P-Selectin

SCR repeat

P-Selectin

Was this article helpful?

0 0
Atkins Low Carb Diet Recipes

Atkins Low Carb Diet Recipes

The Atkins Diet is here. Dr Atkins is known for his great low carb diets. Excluding, Dr Atkins carb counter and Dr Atkins New Diet Revolution.

Get My Free Ebook


Post a comment