PHSI3012 09-2 Vascular Inflammation

Integrins are membrane-bound proteins that are key inflammatory proteins. They’re heterodimers with α and β subunits. They include αLβ2, VLA-1, α4β1, LFA-1. Three integrin conformations have been described (bent form with closed headpiece; extended form with closed headpiece; extended form with open headpiece). Of these, the Bent with closed headpiece Extended with closed headpiece Extended with open headpiece( Bent with closed headpiece, Extended with closed headpiece, Extended with open headpiece ) is the only one with HIGH affinity for ligand.
They can be activated by either chemokine engagement or selectin engagement. One results in rolling SLOWING, the other in it STOPPING. Which stops it? Chemokine engagement Selectin engagement( Chemokine engagement, Selectin engagement ).

CAMs include Intercellular (ICAM) and Vascular (VCAM). (and others)
VCAM-1 ICAM-1( VCAM-1, ICAM-1 ) is predominantly expressed on endothelial cells, but is also present on SMCs. Binds to VLA1 (Very Late Antigen-1) and α4β1 integrins.
ICAM-1 VCAM-1( ICAM-1, VCAM-1 ) is expressed on endothelial cells but also on leukocytes including neutrophils and monocytes.
Both are produced by inflammation but ICAM-1 VCAM-1( ICAM-1, VCAM-1 ) is more constitutively expressed

TRAIL = Tumour necrosis-factor Related Apoptosis-Inducing Ligand.
It’s a member of the TNF NFKB ICAM-1 VCAM-1 PSGL1 ESL-1 ELS-1( TNF, NFKB, ICAM-1, VCAM-1, PSGL1, ESL-1, ELS-1 ) ligand family.
Causes apoptosis of cancer/tumour cells; in clinical trials for cancer therapy. Emergence of non-apoptotic functions in normal cell.

Trail-/- (complete knockout) mice develop PVD and have Impaired Restored( Impaired, Restored ) vascularity in reponse to ischaemia.