HMB435H1 Lecture Notes - Icam2, Vcam-1, Icam-1

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Published on 24 Dec 2010
School
UTSG
Department
Human Biology
Course
HMB435H1
Professor
Integrin and leukocyte moving: Cybalsky lecture
Leukocyte emigration can be subdivided into a series of steps or stages:
tethering/rolling (transient adhesive interactions)
arrest
Firm or stable adhesion (leukocyte flattening or spreading)
Intravascular crawlin g
transendothelial migration or diapedesis (migration between or through endothelial cells)
Endothelial Cell Activation
Inflammatory IL-1/TNFa a c tivate endothelial cells to express adhesion molecules:
Selectins: (E-selectin), platelet (P-selectin) and leukocyte (L-selectin)
Selectin ligands: sLeX on PSGL-1
Immunoglobulin gene superfam ily: ICAM-1, ICAM-2, VCAM-1
Integrins: 2 and 4
Selectins and ligands:
Contain a calcium-dependent lectin domain with an adjacent EGF-like domain
The lectin domain binds a small carbohydrate molecule called sialylated Lewis X or sLeX
sLeX is expressed on glycoproteins like mucins, where serine/threonine are glycosylated (O-
linked).
PSGL-1 is the main leukocyte ligand of endothelial cell selectins
PSGL-1 is expressed on leukocyte microvilli
Optimal P-selectin binding requires tyrosine sulfation of PSGL-1 near its amino terminus
Selectins mediate leukocyte rolling
Immunoglobulins (Ig): ICAM-1, ICAM-2, VCAM-1 and PECAM-1 ligands
Type 1 transmembrane glycoproteins containing Ig homology domains
ICAM-1, VCAM-1 binds leukocyte integrins and mediates arrest, adhesion and intravascular
crawling.
Function of Integrins on Anchorage-Dependent Cell
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Document Summary

Leukocyte emigration can be subdivided into a series of steps or stages: tethering/rolling (transient adhesive interactions) arrest. Firm or stable adhesion (leukocyte flattening or spreading) Intravascular crawling transendothelial migration or diapedesis (migration between or through endothelial cells) Inflammatory il-1/tnfa activate endothelial cells to express adhesion molecules: Contain a calcium-dependent lectin domain with an adjacent egf-like domain. The lectin domain binds a small carbohydrate molecule called sialylated lewis x or slex slex is expressed on glycoproteins like mucins, where serine/threonine are glycosylated (o- linked). Psgl-1 is the main leukocyte ligand of endothelial cell selectins. Optimal p-selectin binding requires tyrosine sulfation of psgl-1 near its amino terminus. Immunoglobulins (ig): icam-1, icam-2, vcam-1 and pecam-1 ligands. Type 1 transmembrane glycoproteins containing ig homology domains. Icam-1, vcam-1 binds leukocyte integrins and mediates arrest, adhesion and intravascular crawling. Integrins provide a link between the cell cytoskeleton and the extracellular matrix. Integrins are clustered in focal adhesion complexes as signaling molecules.