E-selectin
E-selectin, also known as CD62 antigen-like family member E (CD62E), endothelial-leukocyte adhesion molecule 1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a cell adhesion molecule expressed only on endothelial cells activated by cytokines. Like other selectins, it plays an important part in inflammation. In humans, E-selectin is encoded by the SELE gene.[1]
Ligands
E-selectin recognizes and binds to sialylated carbohydrates present on the surface proteins of certain leukocytes. These carbohydrates include members of the Lewis X and Lewis A families found on monocytes, granulocytes, and T-lymphocytes.[2]
Function
During inflammation, E-selectin plays an important part in recruiting leukocytes to the site of injury. The local release of cytokines IL-1 and TNF by damaged cells induces the over-expression of E-selectin on endothelial cells of nearby blood vessels.[2] Leukocytes in the blood expressing the correct ligand will bind with low affinity to E-selectin, causing the leukocytes to "roll" along the internal surface of the blood vessel as temporary interactions are made and broken.
As the inflammatory response progresses, chemokines released by injured tissue enter the blood vessels and activate the rolling leukocytes, which are now able to tightly bind to the endothelial surface and begin making their way into the tissue.[2]
P-selectin has a similar function, but is expressed on the endothelial cell surface within minutes as it is stored within the cell rather than produced on demand.[2]
Pathological relevance
In cases of elevated blood glucose levels, such as in sepsis, E-selectin expression is higher than normal, resulting in greater microvascular permeability. The greater permeability leads to edema of the skeletal endothelium, resulting in skeletal muscle ischemia and eventually necrosis. This underlying pathology is the cause of the symptomatic disease critical illness polyneuromyopathy (CIPNM).[3] Traditional Chinese herbal medicines, like berberine downregulate E-selectin.[4]
E-selectin is also an emerging biomarker for the metastatic potential of some cancers including colorectal cancer and recurrences.[5]
References
- ^ Collins T, Williams A, Johnston GI, Kim J, Eddy R, Shows T, Gimbrone MA, Bevilacqua MP (February 1991). "Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1". J. Biol. Chem. 266 (4): 2466–73. PMID 1703529.
- ^ a b c d Cotran; Kumar, Collins. Robbins Pathologic Basis of Disease. Philadelphia: W.B Saunders Company. ISBN 0-7216-7335-X.
- ^ Visser LH (November 2006). "Critical illness polyneuropathy and myopathy: clinical features, risk factors and prognosis". Eur. J. Neurol. 13 (11): 1203–12. doi:10.1111/j.1468-1331.2006.01498.x. PMID 17038033.
- ^ Hu Y, Chen X, Duan H, et al. (Oct 2009) "Chinese herbal medicinal ingredients inhibit secretion of IL-6, IL-8, E-selectin and TXB2 in LPS-induced rat intestinal microvascular endothelial cells." Immunopharmacol Immunotoxicol. 2009;31(4):550-5. Summary PMID=19874221
- ^ Sato H, Usuda N, Kuroda M, Hashimoto S, Maruta M, Maeda M. (June 2010). "Significance of Serum Concentrations of E-selectin and CA19-9 in the Prognosis of Colorectal Cancer". Japanese Journal of Clinical Oncology 40 (11): 1073–1080. doi:10.1093/jjco/hyq095. PMID 20576794. http://jjco.oxfordjournals.org/cgi/content/abstract/hyq095v1.
Further reading
External links
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PDB gallery
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1esl: INSIGHT INTO E-SELECTIN(SLASH)LIGAND INTERACTION FROM THE CRYSTAL STRUCTURE AND MUTAGENESIS OF THE LEC(SLASH)EGF DOMAINS
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1g1t: CRYSTAL STRUCTURE OF E-SELECTIN LECTIN/EGF DOMAINS COMPLEXED WITH SLEX
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| 1-50 |
CD1 ( a-c, 1A, 1D, 1E) · CD2 · CD3 ( γ, δ, ε) · CD4 · CD5 · CD6 · CD7 · CD8 ( a) · CD9 · CD10 · CD11 ( a, b, c) · CD13 · CD14 · CD15 · CD16 ( A, B) · CD18 · CD19 · CD20 · CD21 · CD22 · CD23 · CD24 · CD25 · CD26 · CD27 · CD28 · CD29 · CD30 · CD31 · CD32 ( A, B) · CD33 · CD34 · CD35 · CD36 · CD37 · CD38 · CD39 · CD40 · CD41 · CD42 ( a, b, c, d) · CD43 · CD44 · CD45 · CD46 · CD47 · CD48 · CD49 ( a, b, c, d, e, f) · CD50
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| 51-100 |
CD51 · CD52 · CD53 · CD54 · CD55 · CD56 · CD57 · CD58 · CD59 · CD61 · CD62 (E, L, P) · CD63 · CD64 ( A, B, C) · CD66 ( a, b, c, d, e, f) · CD68 · CD69 · CD70 · CD71 · CD72 · CD73 · CD74 · CD78 · CD79 ( a, b) · CD80 · CD81 · CD82 · CD83 · CD84 · CD85 ( a, d, e, h, j, k) · CD86 · CD87 · CD88 · CD89 · CD90 · CD91- CD92 · CD93 · CD94 · CD95 · CD96 · CD97 · CD98 · CD99 · CD100
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| 101-150 |
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| 151-200 |
CD151 · CD152 · CD153 · CD154 · CD155 · CD156 ( a, b, c) · CD157 · CD158 ( a, d, e, i, k) · CD159 ( a, c) · CD160 · CD161 · CD162 · CD163 · CD164 · CD166 · CD167 ( a, b) · CD168 · CD169 · CD170 · CD171 · CD172 ( a, b, g) · CD174 · CD177 · CD178 · CD179 ( a, b) · CD181 · CD182 · CD183 · CD184 · CD185 · CD186 · CD191 · CD192 · CD193 · CD194 · CD195 · CD196 · CD197 · CDw198 · CDw199 · CD200
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| 201-250 |
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| 251-300 |
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| 301-350 |
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