The selecting: vascular adhesion molecules

Abstract

The selectin family of adhesion molecules mediates the initial attachment of leukocytes to venular endothelial cells before their firm adhesion and diapedesis at sites of tissue injury and inflammation. The selectin family consists of three closely related cell-surface molecules with differential expression by leukocytes (L-selectin), platelets (P-selectin), and vascular endothelium (E- and P-selectin). The selectins have characteristic extracellular regions composed of an amino-terminal lectin domain that binds a carbohydrate ligand, an epidermal growth factor-like domain, and two to nine short repeat units homologous to domains found in complement binding proteins. In contrast to most other adhesion molecules, selectin function is restricted to leukocyte interactions with vascular endothelium. Multiple studies indicate that the selectins mediate neutrophil, monocyte, and lymphocyte rolling along the venular wall. The generation of selectin-deficient mice has confirmed these findings and provided further insight into how the overlapping functions of these receptors regulate inflammatory processes. Selectin-directed therapeutic agents are now proven to be effective in blocking many of the pathological effects resulting from leukocyte entry into sites of inflammation. Future studies are focused on how the selectins interact with the increasing array of other adhesion molecules and inflammatory mediators.

The response of human bone marrow to chronic cigarette smoking

“…There is a growing body of evidence that PMNLs released from activated bone marrow are more harmful to the host [20,24,28,35,36]. L-selectin initiates the adherence of PMNLs to endothelium under conditions of flow and has been shown to be important for the recruitment of PMNLs to inflamed tissue [37,38]. DOYLE et al [39] have shown that L-selectin contributes to the prolonged sequestration of PMNLs in lung capillaries.…”

Endothelial cell functions

“…L-selectin is a major carbohydrate-presenting ligand for E-selectin on human neutrophils identified in vitro but the actual in vivo ligand may be an unique mucin modified with N-linked sugars that has been characterized in murine cells and called E-selectin ligand-1 (Willmroth and Beaudet, 1999). L-selectin binds to at least three glycoproteins: Gly-CAM-1, CD-34, and MAdCAM-1 which are expressed on the endothelial cell surface, the most probable being a fucosylated variant of CD34 (Tedder et al, 1995;Varki, 1997). P-selectin interacts with its leukocyte counterpart, P-selectin glycoprotein ligand-1 (PSGL-1) which is, like CD34, modified with O-linked sialic acid and fucose (McEver and Cummings, 1997).…”

Inhibition of Lipopolysaccharide Activity by a Bacterial Cyclic Lipopeptide Surfactin

“…The most important of the adhesion molecules involved in this process are intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin [8,9]. Without stimulation, only a small amount of ICAM-1 is present on the endothelial cell surface [10], and VCAM-1 and E-selectin are absent entirely [11,12], but they are immediately expressed in response to extracellular inflammatory stimulation [13]. ICAM-1 interacts with the ligand CD11a/CD18 (LFA-1), which is expressed on neutrophils, lymphocytes, and monocytes; and VCAM-1, with the ligand VLA-4, which is expressed on lymphocytes.…”