SAQ: Processes of leukocyte recruitment

Question 1

Inflammation response

Answer 1

• Occurs in minutes to hours
• Observable microscopically
• Leukocyte recruitment
• Vessel permeability

Question 2

1. Endothelial Activation

Answer 2

• TNF-α
• IL-1β
• E. coli lipopolysaccharide
• NFκB-dependent transcription of CAMs
• Chemokines are released from endothelium when activated by inflammatory molevcules
• Circulating leukocytes are attracted by chemokine concentration gradient

Question 3

2. Capture/rolling

Answer 3

EC surface adhesion receptors
- E-Selectin, P-Selectin

Leukocyte complementary ligands

• L-Selectin
• E-Selectin ligand-1
• PSGL-1 (PS glycoprotein ligand)
• CD44, CD43

Question 4

3. Arrest

Answer 4

• EC-surface chemokines activate VLA4
• β1 Integrin binds VCAM-1
• β2 Integrin binds ICAM-1

Question 5

4. Flattening/crawling

Answer 5

• Possibly flatten to reduce shear stress from blood flow
• β1/2-Integrins- V/I CAM-1 interaction
• β2 interaction thought to control crawling

Question 6

5. Transendothelial migration

Answer 6

• Leukocyte interacts with many EC surface receptors:
  ICAM-1, VCAM-1, PECAM-1, CD47, E-selectin
• Intracellular signalling
• Receptors associate with cytoskeleton via adapter proteins
• Leukocytes can migrate in paracellular or transcellular fashion