L19: Leukocyte migration Flashcards
What are CAMs?
Cell adhesion molecules that are on epithelial tissues
What structure is responsible for initial attachment of leukocytes to endothelial cells?
selectins
Describe selectin structure. Where is it found. What does it bind to?
Has a lectin domain. Found on epithelial tissues. CHO domains on mucins
What are mucins? What do they bind to? Where are they found?
glycosylated proteins.
Binds to selectins and other mucins
Found on leukocytes
What are integrins?
Heterodimer proteins found in leukocytes.
What are ICAMs? What do they bind to?
CAMs with IG domain. Binds to integrins
What are madCAMs? Where are they found? What do they bind to?
CAMs with IG and mucin domains. Found in mucosal endothelial. Binds to integrins on lymphocytes
What is tethering and rolling mediated by?
Selectins
Selectin binding requires what?
Ca2+
What could possibly be pulling leukocytes towards farther epithelial cells during rolling?
A whip like throw of actin filament
Are selectins specific to carbohydrate types?
Yes they are very selective.
Do epi cells always produce E-selectins? If not, what triggers them?
No. Cytokines
What is a type of sugar selectins bind to? Where is this found. How many carbons does it have?
Sialyl Lewis X. End of glycoproteins or glycolipids. It is a 9 carbon monosaccharide
How can we see leukocyte movement in blood vessel?
Intravital microscopy. Cut blood vessels out of mice. ew.
How do integrins form various types of specificity?
Multiple alpha and beta subunits combination
Which Beta subunit is responsible for leukocyte and epithelial cell adhesion? Which alpha unit does it bind with? What is this named?
β4. αL. LFA-1
Is the sialyl lewis X sugar binding to E selectin a tight bound?
No. It unbinds every so often to allow rolling instead of a tight adhesion.
What are two types of signalling in integrin activation? Which one is important in leukocyte migration?
Inside out (talin) >> important for leukocyte migration outside in (fibronogen)
Describe inside out integrin activation.
Talin binds to intracellular subunits and separates them. This conformational change (flailing out of extracellular domain) allows stronger ligand binding
How can we check that inside out activation of integrin is essential?
Truncate cytoplasmic tail to disallow inside out signalling and see what happens
What can increase activation of talin in leukocyte LFA1 pathway?
IL8
What are two types of CAM? Which has homotypic and heterotyopic binding?
N-CAM (homo) and I-CAM (hetero)
Are CAMs Ca2+ depended?
No
Tight adhesion is done by which two mechanisms?
I-CAM + LFA1
IL8 + IL8R
IL8R is on the leukocyte or the epi cell?
leukocyte
What are two types of diapedesis?
Paracellular.
Transcellular
Which molecule is responsible for paracellular diapedesis? What is it normally a part of?
Jam-1. Tight junction
What happens in the absence of Jam-1?
No paracellular diapedesis
Is transcellular diapedesis due to physical or chemical change?
Mostly physical. But chemical changes happen in response to the physical interactions.
Describe the effects and pathways in epi cells when leukocytes dock on epi cells.
NPF > Arp2/3 > actin poly
PIP2 > Cdc42 > Arp2/3
WAVE2 > Arp2/3
What happens in the absence of WAVE2?
fewer transcellular diapedesis
How do leukocytes look for the easiest way for entry during transcellular diapedesis?
Yes. They probe with invadopodia like protrusions
How do MMPs help in crossing the basal membrane?
MMPs are not needed. Somehow these cells can pass right through. Cancer cells do the same
