Question

What it means by rolling white blood cell? What are the steps in the process? What types of material mediate each step?

Answer 1

White blood cells (leukocytes) perform most of their functions in tissues. Functions include phagocytosis of foreign particles, production of antibodies, secretion of inflammatory response triggers (histamine and heparin), and neutralization of histamine. In general, leukocytes are involved in the defense of an organism and protect it from disease by promoting or inhibiting inflammatory responses. Leukocytes use the blood as a transport medium to reach the tissues of the body.

Here is a brief summary of each of the four steps currently thought to be involved in leukocyte extravasation:

Chemoattraction

Upon recognition of and activation by pathogens, resident macrophages in the affected tissue release cytokines such as IL-1, TNFα and chemokines. IL-1, TNFα and C5a cause the endothelial cells of blood vessels near the site of infection to express cellular adhesion molecules, including selectins. Circulating leukocytes are localised towards the site of injury or infection due to the presence of chemokines.

Rolling adhesion

Like velcro, carbohydrate ligands on the circulating leukocytes bind to selectin molecules on the inner wall of the vessel, with marginal affinity. This causes the leukocytes to slow down and begin rolling along the inner surface of the vessel wall. During this rolling motion, transitory bonds are formed and broken between selectins and their ligands.

For example, the carbohydrate ligand for P-selectin, P-selectin glycoprotein ligand-1 (PSGL-1), is a expressed by different types of leukocytes (white blood cells). The binding of PSGL-1 on the leukocyte to P-selectin on the endothelial cell allows for the leukocyte to roll along the endothelial surface. This interaction can be tuned by the glycosylation pattern of PSGL-1, such that certain glycovariants of PSGL-1 will have unique affinities for different selectins, allowing in some cases for cells to migrate to specific sites within the body (e.g. the skin).

Tight adhesion

At the same time, chemokines released by macrophages activate the rolling leukocytes and cause surface integrinmolecules to switch from the default low-affinity state to a high-affinity state. This is assisted through juxtacrine activation of integrins by chemokines and soluble factors released by endothelial cells. In the activated state, integrins bind tightly to complementary receptors expressed on endothelial cells, with high affinity. This causes the immobilisation of the leukocytes, despite the shear forces of the ongoing blood flow.

Transmigration

The cytoskeletons of the leukocytes are reorganised in such a way that the leukocytes are spread out over the endothelial cells. In this form, leukocytes extend pseudopodia and pass through gaps between endothelial cells. Transmigration of the leukocyte occurs as PECAM proteins, found on the leukocyte and endothelial cell surfaces, interact and effectively pull the cell through the endothelium. Once through the endothelium, the leukocyte must penetrate the basement membrane. The mechanism for penetration is disputed, but may involve proteolytic digestion of the membrane, mechanical force, or both.The entire process of blood vessel escape is known as diapedesis. Once in the interstitial fluid, leukocytes migrate along achemotactic gradient towards the site of injury or infection.