Adhesion Molecules On Leukocytes And Endothelial Cells Involved In Leukocyte Recruitment

The migration of leukocytes from the blood into tissues involves adhesion between the circulating leukocytes and vascular endothelial cells as a prelude to the movement of the leukocytes out of the vessels into the tissues. This adhesion is mediated by two classes of molecules, called selectins and integrins, and their ligands. The expression of these molecules varies among different types of leukocytes and in blood vessels at different locations. We next describe the major selectins and integrins and their ligands and their roles in leukocyte recruitment into tissues.

Selectins and Selectin Ligands

Selectins are plasma membrane carbohydrate-binding adhesion molecules that mediate an initial step of low-affinity adhesion of circulating leukocytes to endothelial cells lining postcapillary venules (Table 3-1). The extracellular domains of selectins are similar to C-type lectins, so called because they bind carbohydrate structures (the definition of lectins) in a calcium-dependent manner. Selectins and their ligands are expressed on leukocytes and endothelial cells.

Two types of selectins are expressed by endothelial cells, called P-selectin (CD62P) and E-selectin (CD62E). P-selectin, so called because it was first found in platelets, is stored in cytoplasmic granules of endothelial cells and is rapidly redistributed to the surface in response to microbial products, cytokines, histamine from mast cells, and thrombin generated during blood coagulation. E-selectin is synthesized and expressed on the endothe-lial cell surface within 1 to 2 hours in response to the cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF) and microbial products such as lipopolysaccharide (LPS). We will discuss IL-1, TNF, and LPS in our discussion of inflammation in Chapter 4.

The ligands on leukocytes that bind to E-selectin and P-selectin on endothelial cells are complex sialylated carbohydrate groups related to the Lewis X or Lewis A family, present on various surface glycoproteins of granu-locytes, monocytes, and some previously activated effector and memory T cells. The best defined of these is the tetrasaccharide sialyl Lewis X (sLeX). A leukocyte membrane glycoprotein called P-selectin glycoprotein ligand 1 (PSGL-1) is post-translationally modified to display the carbohydrate ligands for P-selectin. Several different

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