Selectins roles

Integrins, ICAMS, and Selectins Role and Regulation of Adhesion Molecular in Neutrophil Recruitment to Inflammatory Sites Takashi Kai Kishimoto and Robert Rothlein... 

G. Mannori, P. Crottet, O. Cecconi, K. Hanasaki, A. Aruffo, R.M. Nelson, A. Varki and M.P. Bevilacqua, Differential coloncancer cell adhesion to E-, P-, and L-selectin role of mucin-type glycoproteins. Cancer Res., 55 (1995) 4425-4431. 

Cell Adhesion. The membranes of leukocytes and platelets contain a variety of components that promote ceU-surface contact. Although numerous ceU-surface molecules are likely to play a role in ceU-surface adhesion, the group of selectins are of particular interest to research on this subject. Selectins are molecules that are known to promote leukocyte—platelet adhesion. However, selectin-based models have not been able to account for the fact that platelets are allowed to pass through the filter and leukocytes are not. 

Selectins Play Key Roles in Inflammation in Lymphocyte Homing... 

Oxidatively modified LDL up-regulates the surfece expression of VCAM-1 and intracellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells, promoting the interactions between both cell types (Kume et al., 1992). This may play a pivotal role in the development of atherosclerosis by promoting the penetration of circulating monocytes into the suben-dothelial space whilst inhibiting the mobility of resident macrophages. It has been previously demonstrated that ICAM-1, E-selectin, and VCAM-1 are up-regulated in the microvasculature of rheumatoid but not control synovium (Corkill et al., 1991 Koch et al., 1991). The association between ox-LDL and increased expression of adhesion molecules in the inflamed synovium has yet to be studied. 

Fig. 4. The role of RANTES in recruiting monocytes and T lymphocytes to injured endothelium involves the binding of platelets to activated endothelium in a P-selectin-dependent manner with subsequent secretion of RANTES by bound platelets. RANTES can then attract CCR5-expressing monocytes and T cells to the damaged endothelium as well as causing monocyte firm adhesion to occur via binding to platelet-derived RANTES deposited on the endothelial cell layer.

Nemmar, A. et al. (2007) Enhanced peripheral fhrombogenidty after lung inflammation is mediated by platelet-leukocyte activation role of P-selectin. Journal of Thrombosis and Haemostasis,... 

Masamune, A., Igarashi, Y. and Hakomori, S.. 1996, Regulatory role of ceramide in interleukin (IL)-1 -induced E-selectin expression in human umbilical vein endothehal cells. Ceramide errhances IL-1 action, but is not sufficient for E-selectin expression. J. 

McEver RP, Cummings RD. Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest 1997 100 S97-S103. 

Platelets also express adhesion receptors of the selectin gene family (P-selectin) and of the immunoglobulin gene superfamily (PECAM-1 and ICAM-2) (6). Expression of PECAM-1 and ICAM-2 may play a role in platelet interactions with endothelial cells and leukocytes, respectively. 

Aplin, A.E., Howe, A., Alahari, S.K., Jiiliano, R.L. (1998) Signal transduction and signal modulation by cell adhesion receptors the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacol. Rev. 50, 197-263. 

Lex-antigenic trisaccharide (a-L-Fuc(l-3)-[p-D-Gal-(l-4)-p-D-GlcNAc]) and its sialylated structure (SLex) are terminal components of a nnmber of glycoconjugates on cell surfaces [31]. SLex serves as a ligand for the endothelial leukocyte molecule-1 (E-selectin) [32], which mediates the initial stages of adhesion of leukocytes to activated endothelial cells, and pays a critical role during inflammatory responses [33]. Lex-based carbohydrates have shown promise in therapeutic investigations related to the inflammatory process. As a result, extensive efforts have been directed toward the synthesis of SLex and related molecules [34 also see Chap. 15],... 

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. 

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