L selectin

In the very early phases of the acute inflammatory response most of the cells invading the damaged area are polymorphonuclear neutrophils, also denoted as PMNs, which serve as initial line of defense and source of proinflammatory cytokines. These cells, which usually live for 4-5 days, circulate in the blood until they are attracted by chemokines into injured tissues. Whereas physical injury does not recruit many neutrophils, infections with bacteria or fungi elicit a striking neutrophil response. The characteristic pus of a bacterial abscess is composed mainly of apoptotic (apoptosis) and necrotic PMNs. Emigration of neutrophils from the blood starts with a process denoted as margination where neutrophils come to lie at the periphery of flowing blood cells and adhere to endothelial cells (Fig. 1). L-Selectin is expressed... 

Selectins L-selectin PMN, lymphs CD34,Gly-CAM-L Sialyl-Lewis" and others... 

These are ligands for lymphocyte L-selectin the ligands for neutrophil L-selectin have not been identified. 

Figure 47-10. Schematic diagram of the structure of human L-selectin. The extracellular portion contains an amino terminal domain homologous to C-type lectins and an adjacent epidermal growth factor-like domain. These are followed by a variable number of complement regulatory-like modules (numbered circles) and a transmembrane sequence (blackdiamond). A short cytoplasmic sequence (open rectangle) is at the carboxyl terminal. The structures of P- and E-selectin are similar to that shown except that they contain more complement-regulatory modules.The numbers of amino acids in L-, P-, and E- selectins, as deduced from the cDNA sequences, are 385,789, and 589, respectively. (Reproduced, with permission, from Bevilacqua MP, Nelson RM Selectins. J Clin Invest 1993 91 370.)...

Baumheter S, Singer MS, Henzel W, Hemmerich S, Renz M, Rosen SD, Lasky LA (1993) Binding of L-selectin to the vascular sialomucin CD34. Science 262(5132) 436-438... 

LPS Lipopolysaccharide L-selectin Leucocte selectin, formerly knovm as monoclonal antibody that recognizes murine L-selectin (MEL-14 antigen), leucocyte cell adhesion molecule-1 (LeuCAM-1), lectin cell adhesion molecule-1 (LeCAM-1 or LecCAM-1), leucocyte adhesion molecule-1 (LAM-1)... 

Smalley DM, Ley K. L-selectin mechanisms and physiological significance of ectodomain cleavage. J Cell Mol Med 2005 9 255-266. 

A Compound P-selectin (IC50 mM) L-selectin (IC50 mM) E-selectin (IC50 mM)... 

The interest in using saccharide-substituted polymers to bind and cluster cell surface proteins arises from studies of L-selectin, a protein involved in inflammation. L-selectin binds glycoproteins that display complex carbohydrates, and... 

Tsuji, T., et al. Efficient induction of immunoglobulin production in neonatal naive B cells by memory CD4+ T cell subset expressing homing receptor L-selectin, J. Immunol., 152, 4417, 1994. 

On the neutrophil, the major selectin expressed is L-selectin. This molecule is constitutively expressed on mature neutrophils but may be expressed at low levels (50% of adult) in neonates. Stimulation of endothelial cells with thrombin, histamine, IL-1 and some other agents induces neutrophils (and other leukocytes) to leave the circulation and adhere to the endothelium. They do this by rolling onto the surface of the endothelium, to which they attach via P-selectin translocated from storage sites in Weibel-Palade bodies to the surface of the endothelium upon activation. The expression of P-selectin is short-lived and is replaced on the endothelial surface by E-selectin (whose expression is also regulated by some cytokines), which continues the endothelial-leukocyte interaction. 

After the initial attachment of neutrophils to the endothelium via the selec-tins, the next stage in the process is performed via the integrins. L-selectin on the neutrophil surface is shed (the shed molecule being some 8-10 kDa smaller than the bound molecule) via a process that probably involves proteolytic cleavage. The major groups of integrins present on leukocytes are shown in Table 3.2 further properties of these molecules are given later. 

Harms G, Kraft R, Grelle G, Volz B, Dernedde J, Tauber R (2001) Identification of nucleolin as a new L-selectin ligand. Biochem J 360 531-538... 

Szabo, G., Jr., Pine, P. S., Weaver, J. L., Rao, P. E., and Aszalos, A. (1994) The L-selectin (Leu8) molecule is associated with the TcR/CD3 receptor fluorescence energy transfer measurements on live cells. Immunol. Cell Biol. 72, 319-325. 

The recruitment and migration of leucocytes into inflamed tissues is a carefully orchestrated process (Figure 7.1). It consists of sequential steps mediated by different families of adhesion molecules expressed by both the leucocytes and the endothelial cells at the site of inflammation [4]. Of these adhesion molecules, the selectin family mediates the initial contact and subsequent rolling of the leucocyte on the endothelium. It consists of three members, i.e. E- (endothelial), P- (platelet) and L- (leucocyte) selectin. Activated endothelial cells express E- and P-selectin. P-selectm is also expressed on platelets, whereas L-selectin is only expressed on subsets of leucocytes [5]. 

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