CHEMICAL MEDIATORS IN ACUTE INFLAMMATION.ppt

Chemical mediators in Acute Inflammation

1. Chemical Mediators of
Inflammation
These are a large and heterogenous
group of endogenous compounds that
increase vascular permeability.
Other actions include vasodilation,
chemotaxis, fever, pain and tissue
damage.

3. Vasoactive amines
These are 2 substances Histamine and
Serotonin which play an early role – first 1hr.
Histamine – is stored in mast cells, basophils
and platelets.
Released by various stimuli such as heat, cold,
radiation, trauma, chemicals, Ag-Ab Rx., C3a,
C5a, IL, Substance P etc.
Main actions are VD, ^ V.P, pain and itching

4. Vasoactive amines
Serotonin – 5HT. – Present in tissues such as
chromaffin cells of GIT, spleen, nervous system,
mast cells and platelets.
Actions are similar as Histamine but less
pronounced.

5. Arachidonic Acid (AA)
metabolites
AA is a fatty acid called eicosa-tetra-enoic
acid (ETE)
Its sources are from the diet and from
conversion of linoleic acid to AA.
AA must first be activated by C5a to form
its metabolites
AA metabolites are formed by 2 pathways

6. Arachidonic Acid (AA)
metabolites
AA metabolites are formed by 2 pathways
1. Cyclo-oxygenase pathway
( Prostaglandins, ThromboxaneA2, Prostacyclin)
2. Lipo-oxygenase pathway
( Leukotrienes or Slow reacting substances (SRS)

7. Cyclo-oxygenase pathway

8. Lipo-oxygenase pathway

9. Lysosomal components
These are substances released by neutrophils and
monocytes
Neutrophils – Azurophilic granules release MPO, acid
hydrolases, elastase, collagenase and protease
Neutrophils - Specific granules contain lactoferrin,
lysozyme, alkaline phosphatase and collagenase
Monocytes – acid proteases, collagenase, elastase and
plasminogen activator

10. Platelet activating factor (PAF)
Released from IgE sensitised basophils or
mast cells, other leucocytes, endothelium
and platelets.
Actions are Platelet aggregation, release
reaction, ^ V.P, VD, B.C, leucocyte
adhesion, chemotaxis

11. Cytokines
These are polypeptide substances produced by
activated lymphocytes (lymphokines) and monocytes
(monokines).
They may act on itself or other cells
Main cytokines are IL-1, TNF-a and TNF-b, IF-g, and
chemokines IL-8, PF-4.
IL-1 and TNF-a – produced by activated macrophages
TNF-b, IF-g – activated T cells
Chemokines – IL-8 (macrophages), PF-4 (platelets)

12. Actions of Cytokines
IL-1 & TNF-a, TNF-b - ^ leucocyte adherence,
thrombogenecity, secretion of other cytokines,
acute phase reactions
IF-g – causes activation of macrophages &
neutrophils, synthesis of NO synthase
Chemokines act as chemotactic factors for
neutrophils ( IL-8), monocytes ( PF-4, MCP-1),
eosinophils (eotaxin)

13. Nitric Oxide
Liberated by endothelial cells
Causes VD, anti-platelet activation,
microbicidal action.

14. PLASMA PROTEASES
These are substances derived from 4
systems
The kinin system
The clotting system
The fibrinolytic system
The complement system

15. PLASMA PROTEASES
These are products derived from
activation of 4 interlinked systems
The kinin system
The clotting system
The fibrinolytic system
The complement system
The key role is played by the Hageman Factor
(Factor XII)

16. 4 interlinked systems

17. The kinin system

18. The kinin system
Effects of Bradykinin
Smooth muscle contraction
Vasodilation
Increased Vascular Permeability
Pain

19. The Clotting System

20. The Clotting System
Actions of Fibrinopeptides
Increased Vascular permeability
Chemotaxis
Anticoagulant activity

21. The Fibrinolytic System

22. The Fibrinolytic system
The actions of Plasmin are
Activation of Factor XII
Splits off C3 to form C3a which is an opsonin
Degrades fibrin to form fibrin split products
(FDP) which ^ V.P and chemotaxis

23. The Complement System
Activation of this system can occur by 2 pathways
Classic Pathway (Ag-Ab reactions)

Alternate Pathway (Bacterial toxins, cobra venom)
The end products by either of these pathways are
anaphylatoxins (C3a, C4a, C5a) and Membrane attack
complex (MAC).
Actions of anaphylatoxins are
 release of histamine from mast cells and basophils
 increased vascular permeability
 phagocytosis (C3b)
 Chemotaxis (C5a)
 Cell membrane damage (MAC)