Selectins are a family of cell adhesion
molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminusand 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 sugar moietiesand so are considered to be a type of lectin, cell adhesion proteins that bind sugar polymers. [Parham,Peter.The Immune System. 2nd ed. Garland Science: New York, 2005. pg. 244-245]
There are three subsets of selectins:
E-selectin(in endothelial cells)
P-selectin(in plateletsand endothelial cells)
The name selectin comes from the words "selected" and "
lectins," which are a type of carbohydrate-recognizing proteins.
During an inflammatory response, stimuli such as
histamineand thrombincause endothelial cells to mobilize P-selectin from stores inside the cell to the cell surface. In addition, cytokinessuch as TNF-alphastimulate the expression of E-selectin and additional P-selectin a few hours later.
As the leukocyte rolls along the
blood vesselwall, the distal lectin-like domain of the selectin binds to certain carbohydrate groups presented on proteins (such as PSGL-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 the leukocyte 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 ]
Selectins are involved in significant
biomedicalresearch. One project involves using selectins in nanodevicesto treat cancer. 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 have covalentlyattached selectins to an epoxysurface in order to encourage tumor cellsand other cells to roll. Also attached to the surface is a ligandthat selectively signals cancer cells to undergo apoptosis, 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 called osteoblastsbecome too scarce. Osteoblasts develop from stem cells, and scientists hope to eventually be able to treat osteoporosisby adding stem cells to a patient’s bone marrow. Researchers have developed a way to use selectins to direct stem cells introduced into the vascular systemto 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 certain glycoproteincauses these cells to migrate to the bone marrow. Thus, selectins may someday be essential to a regenerative therapyfor osteoporosis [ [http://sacksteinlab.bwh.harvard.edu/ Sackstein Lab ] ] .
* [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]
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