Acute inflammatory response Flashcards
Leukocyte diapedesis (passage through walls of capillaries)
- Circulating
- Tethering rolling
- Firm adhesion
- Transmigration
Selectins
Lectin-like adhesion molecules that bind CHO structures (weakly)
Selectins are expressed by
Leukocytes and endothelium
Leukocyte activation leads to
transient increase in avidity and rapid shedding by proteolytic cleavage
Where is P-selectin stored?
Granules
E-selectin expressions is induced by
cytokines or LPS
E-selectin expressions is inhibited by
glucocorticoids
Leukocyte adhesion deficiency-II (LAD-II)
Defective glucose metabolism - leukocytes do no express selectin ligands
Decreased rolling response on E- or P-selectins
Rolling along endothelial cell surface activates
integrins
Leukocyte adhesion deficiency-I (LAD-I)
Leukocytes do not adhere to extracellular material or endothelium in vitro
Leukocytes deficient in beta 2 integrin
Intercellular adhesion molecule-2 (ICAM-2)
Basally expressed on endothelium
Intercellular adhesion molecule-1 (ICAM-1)
Induced by cytokines IL-1, TNF
Natalizumab (Tysabri)
Monoclonal antibody against alpha 4 integrin
Inhibits T lymphocytes interactions with brain endothelium
Transmigration involves
CAMs and chemotaxis (chemoattractants)
Proteases are derived from
plasma zymogens, tissue cells, activated leukocytes
Proteases have a central role in
host defence, inflammation, initiating repair, removal of damaged tissue
3 inter-related plasma derived factors
Complement
Kinin system
Clotting cascade
Angioedema
Deep cutaneous and mucous swelling
ACE inhibitors block
ANGII synthesis - useful in hypertension
Bradykinin degradation - increases inflammation
Treat hereditary angioedema with
Exogenous C1 inhibitor
Bradykinin receptor antagonist (icatibant)
Families of proteolytic enzymes
Matrix metalloproteases (MMP)
Serine proteases
Cysteine proteases
Aspartate proteases
Collagen broken down by
Matrix metalloproteases (MMP) (collagenase)
MMP activated by
removal of propeptide by other proteases
chemical modification of propeptide by RONS
C-terminus of MMP important in
Substrate specificity and regulation
Peptidomimetics
Small hydroxamic acid based molecules
Zinc binding
Based on collagen structure
Inhibit MMP activity
Serine readily inactivated by
oxidation