Selectins L-selectin

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

Selectins are a family of membrane glycoproteins that are divalent cation-dependent and bind to specific carbohydrates containing sialylated moieties. They are composed of leukocyte (L)-selectins, endothelial (E)-selectins and platelet (P)-selectins. L-selectins are expressed on most leukocytes, whereas vascular endothelial cells express E-selectins and P-selectins. Initial binding of leukocytes with vascular endothelium involves selectins and consequently they play an important role in leukocyte trafficking. 

Selectins are cell-adhesion molecules that mediate leukocyte recruitment in irmnune reactions and signal transduction. Selectins comprise three members termed E-, P-, and L-selectin. The CRD is located at the N-terminus, followed by an EGF-hke domain. There are various numbers of consensus repeat sequences following the EGF-like domain. P-selectin, L-selectin and E-selectin contain nine, six, and two repeats, respectively. A transmembrane segment and a cytoplasmic tail are located at the C-terminal. The key domains for target recognition and sugar binding are the N-terminal CRD and EGF-like domain. ... 

The selectin family consists of three members, which are all glycoproteins and which mediate the initial stage of leukocyte adhesion (Fig. 1), namely, L-, E-, and P-selectin. L-selectin is constitutively expressed on the surface of leukocytes. It is involved in the recirculation of lymphocytes in peripheral lymph nodes as well as in the recruitment of leukocytes at the zone of inflammation. E-selectin... 

Lasky, L. A., 1995. Selectin-carbohydrate interactions and the initiation of die inflammatory response. Annual Review of Biochemistry 64 113-139. 

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... 

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)... 

Fig. 1. Surface phenotype of HSPCs. Primitive HSPCs have the phenotype of c-KitThy-ll0WLin CD34+CD33 in humans, and the mouse counterparts have the phenotype of c-KifThy-llowLin Sca-l+. Primitive HSPCs express CXCR4 as the major chemokine receptor and various adhesion molecules such as VLA-4, VLA-5, LFA-1, P-selectin glycoprotein ligand-1 (PSGL-1), and CD44 for migration to the stem cell niche.

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

R2. Rainger, E. S., Wautier, M. P., Nash, G. B., and Wautier, J. L., Prolonged E-selectin induction by monocytes potentiates the adhesion of flowing neutrophil to cultured endothelial cells. Br. J. Haematol. 92,192-199 (1996). 

Bennett, B.L., Cruz, R., Lacson, R.G. and Manning, A.M. (1997) Interleukin-4 suppression of tumor necrosis factor alpha-stimulated E-selectin gene transcription is mediated by STAT6 antagonism of NF-kappaB. Journal of Biological Chemistry 272, 10212-10219. 

Ohno N, Ichikawa H, Coe L, Kvietys PR, Granger DN, Alexander JS. Soluble selectins and ICAM-1 modulate neutrophil-endothelial adhesion and diaped-esis in vitro. Inflammation. 1997 21 313-324. 

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. 

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