- Selectin
Selectins are a family of cell adhesion
molecule s (or CAMs). All selectins are single-chain transmembraneglycoprotein s that share similar properties toC-type lectin s due to a relatedamino terminus and calcium-dependent bindingcite book | title=Robbins Pathologic Basis of Disease| last=Cotran| coauthors=Kumar, Collins| publisher=W.B Saunders Company| location=Philadelphia| id=0-7216-7335-X] . Selectins bind to sugarmoieties and so are considered to be a type oflectin , cell adhesion proteins that bind sugarpolymers . [Parham,Peter.The Immune System. 2nd ed. Garland Science: New York, 2005. pg. 244-245]Types
There are three subsets of selectins:
*E-selectin (in endothelial cells)
*L-selectin (inleukocytes )
*P-selectin (inplatelets and endothelial cells)Etymology
The name selectin comes from the words "selected" and "
lectins ," which are a type of carbohydrate-recognizing proteins.Function
During an inflammatory response, stimuli such as
histamine andthrombin cause endothelial cells to mobilize P-selectin from stores inside the cell to the cell surface. In addition,cytokines such asTNF-alpha stimulate the expression of E-selectin and additional P-selectin a few hours later.As the leukocyte rolls along the
blood vessel wall, the distal lectin-like domain of the selectin binds to certain carbohydrate groups presented on proteins (such asPSGL-1 ) on the leukocyte, which slows the cell and allows it to leave the blood vessel and enter the site of infection. The low-affinity nature of selectins is what allows the characteristic "rolling" action attributed to leukocytes during theleukocyte adhesion cascade ] .The best-characterized ligand for the three selectins is P-selectin glycoprotein ligand-1 (
PSGL-1 ), which is a mucin-type glycoprotein expressed on all white blood cells.Neutrophils and eosinophils bind to E-selectin. One of the reported ligands for E-selectin is the sialylated Lewis X Ag (sLe(x)). Eosinophils, like neutrophils, use sialylated, protease-resistant structures to bind to E-selectin, although the eosinophil expresses much lower levels of these structures on its surface. [cite journal |last=Bochner BS, Sterbinsky SA, Bickel CA, Werfel S, Wein M, Newman W. |title=Differences between human eosinophils and neutrophils in the function and expression of sialic acid-containing counterligands for E-selectin |journal=J Immunol. |volume=152 |issue=2 |date=
Jan 15 ,1994 |pages=774–82 |pmid=7506734 |unused_data=|http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=7506734&query_hl=5&itool=pubmed_docsum ] Ligands for P-selectin on eosinophils and neutrophils are similar sialylated, protease-sensitive, endo-beta-galactosidase-resistant structures, clearly different than those reported for E-selectin, and suggest disparate roles for P-selectin and E-selectin during recruitment during inflammatory responses. [cite journal |last=Wein |first=M |title=Comparison of human eosinophil and neutrophil ligands for P-selectin: ligands for P-selectin differ from those for E-selectin |journal=Am J Respir Cell Mol Biol.|volume=12 |issue=3 |date=1995 |pages=315–9 |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=7532979&query_hl=5&itool=pubmed_docsum ]Research
Selectins are involved in significant
biomedical research. One project involves using selectins innanodevices to treatcancer . Researchers are trying to create a device capable of killing cancer cells circulating in the blood [In the lab of Jeffrey Karp of Harvard Medical School] [ [http://www.karplab.net/ Karp Lab ] ] . The scientists havecovalently attached selectins to anepoxy surface in order to encouragetumor cells and other cells to roll. Also attached to the surface is aligand that selectively signals cancer cells to undergoapoptosis , or cell death. Without selectins, the device would be unable to slow cancer cells down, and would thus be unable to kill them. Selectins are also involved in projects to treat osteoporosis, a disease that occurs when bone-creating cells calledosteoblasts become too scarce. Osteoblasts develop fromstem cells , and scientists hope to eventually be able to treatosteoporosis by adding stem cells to a patient’sbone marrow . Researchers have developed a way to use selectins to direct stem cells introduced into thevascular system to the bone marrow [In the lab of Robert Sackstein Harvard University] . E-selectins are constitutively expressed in the bone marrow, and researchers have shown that tagging stem cells with a certainglycoprotein causes these cells to migrate to the bone marrow. Thus, selectins may someday be essential to aregenerative therapy for osteoporosis [ [http://sacksteinlab.bwh.harvard.edu/ Sackstein Lab ] ] .External links
* [http://www.cimit.org CIMIT Center for Integration of Medicine and Innovative Technology]
* [http://www.karplab.net/ Karp Lab on Research]
* [http://sacksteinlab.bwh.harvard.edu/ Sackstein Lab of Research]
* [http://multimedia.mcb.harvard.edu Computer-generated movie of the mobilization of P-selectin inside a leukocyte at mcb.harvard.edu]References
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