Leukocyte Recruitment

Question 1

“rolling” can be generally described as the

Answer 1

tethering and literal rolling of circulating leukocytes on endothelium through selectin/integrins and their receptors

Question 2

Rolling does what, genrally?

Answer 2

Allows leukocytes to sample endothelial surface for chemokines which activate integrins and trigger adhesion to endothelium

Question 3

Adherent leukocytes do what?

Answer 3

migrate across endothelium to extravascular spaces

Question 4

leukocytes migrate in extravascular tissues via what mechanism?

Answer 4

chemokine gradients

Question 5

Transmigration of Leukocytes: Stages and molecules involved

Answer 5

1. Capture (Selectins)
2. Rolling (Selectins)
3. Activation (Chemokines)
4. Arrest (adhesion molecules VCAM, ICAM etc)
5. Firm adhesion (adhesion molecules VCAM, ICAM)
6. Transmigration (none articulated on image)

Question 6

Transmigration of Neutrophils: overview

Answer 6

1. Activated macs produce TNF/IL-1 –> induce expression of P selectin on surface of endothelia. Can also be E selectin.
2. Interaction between selectin/Sialy lews X ligand initiates rolling
3. L selectin (on neutrophils) binding to ligands on endothelial cells, stabilizes neutrophils
4. Endothelial cells present CXC-chemokine ligand 8 (also called IL-8) that is recognized by neutrophils
5. CCL2 (MCP-1) controls migration of monocytes
6. process activates leukocyte integrins, resulting in better adhesion
7. after migration, they interact with chemokines on basement membrane
8. adopt amoeboid shape
9. migrate along collage fibrils on chemotactic gradient toward site of inflammation
10. chemotactic receptors are on leading edge

Question 7

The different between recruit of neutrophils and monocytes is

Answer 7

identical except for the chemokines involved

neutrophiles = IL-8
monocytes = MCP-1

Question 8

“simplified” version of recruitment

Answer 8

1. Leukocyte is capture and rolls down Selectins
2. As they roll they interact with chemokines
3. chemokine interaction increases integrin affinity for ligand
4. integrin/ligand stabilizes leuk
5. L selectin on leuk further stabilizes leuk
6. transmigration begins
7. chemokines in extravascular space adhere leuks

Question 9

Transmigration of Leukocytes (in steps)

Answer 9

1) capture
2) rolling
3) activation
4) arrest
5) firm adhesion
6) transmigration

Question 10

Which cytokine recruits neutrophils?

Answer 10

Il-8

Question 11

Which cytokine recruits monocytes?

Answer 11

MCP