3. KININ SYSTEM
Activated by Hageman factor (XIIa)
Bradykinin
Potent vasodilator
Increased vascular permeability
Contraction of brochial smooth muscle
Produce pain
Stimulates release of histamine
Activates the arachidonic acid cascade
Short lived because it is quickly inactivated by an
enzyme called Kininase
4. KININ SYSTEM
Kallikrein:
- An enzyme which is active proteolytic form of
prekallikerin.
Actions:
- It converts HMWK into bradykinin.
- Potent activator of Hageman factor (link b/w
kinin & clotting system)
- It has chemotactic activity.
- Also directly converts C5 to C5a.
5. CLOTTING SYSTEM
The intrinsic clotting pathway is activated by Hageman factor
(XII ),which is a protein synthesized by liver in an inactive form.
Hageman factor is activated when it encounters with collagen,
basement membrane & activated platelets.
Factor XII activate XIIa.
XIIa converts prothrombin into thrombin.
Thrombin converts fibrinogen to fibrin & fibrinopeptides ( Increased
Vascular permeability & chemotactic activity).
Thrombin also generates C5a from C5 thus linking coagulation with
complement
7. ARACHIDONIC ACID
METABOLITES
AA is a 20 carbon polyunsaturated fatty acid.
Directly derived from the dietary source or by
conversion from the essential fatty acid linoleic
acid.
Does not occur free in the cell but is esterified in
membrane phospholipids.
Released from membrane phospholipids
through action of cellular phospholipase A2.
Phospholipase A2 is activated by mechanical,
chemical and physical stimuli or by other
mediators, e.g C5a
8. Arachidonic acid metabolites
(EICOSANOIDS)
Synthesize by two major classes of
enzymes:
Cycloxygenase (prostaglandins &
thromboxanes)
Lipoxygenase (leukotrienes & lipoxins)
Found in inflammatory exudate and their
synthesis is increased @ site of
inflammation.
9. Arachidonic acid metabolites
(EICOSANOIDS)
Synthesize by two major classes of
enzymes:
Cycloxygenase (prostaglandins &
thromboxanes)
Lipoxygenase (leukotrines & lipoxins)
Found in inflammatory exudate and their
synthesis is increased @ site of
inflammation.
10.
11. COX-1:
produced in the response to inflammatory
stimuli
- also expressed in most tissues
- Responsible for the production of PGs
-Also serves a homeostatic function. e.g.
fluid and electrolyte balance in the
kidneys, cytoprotection in the GIT.
COX-2:
stimulates the production of PGs and
absent in most tissues under normal
resting conditions.
12. AGENTS SUPPRESSING COX
ACTIVITY
Aspirin and other NSAIDs inhibit PG
synthesis and reduce inflammation but
also predispose to gastric ulceration by
inhibiting COX1
Now highly selective COX-2 inhibitors are
available to preserve the anti inflammatory
effect of COX inhibition
13. LIPOXINS
These are recent addition to the family of
bioactive products generated from AA
prduced by transcellualr biosynthetic
mechanism (involving 2 cell population)
MECHANIM OF ACTION:
- neutrophils produce intermediates in lipoxin
synthesis and these are converted to lipoxins by
platelet interacting with the leukocytes.
- LXA4 & LXB4 are generated by action of platelet
12-lipoxygenase on neutrophil derived LTA4
- cell-cell contact enhance transcellular
metabolism and blocking adhesion inhibits
lipoxin production
14. FUNCTIONS:
- inhibit leukocyte recruitment & the cellular
components of inflammation
- inhibit neutrophil chemotaxis and
adhesion to endothelium
Lipoxins are endogenous –ve regulator of
leukotrien’s action thus play a role in
resolving inflammation
16. – Derived directly from dietary
sources or by conversion of
essential fatty acid linoleic acid
Esterified in membrane
phospholipids
– Must first be released from
phospholipids
Via activation of cellular
phospholipases
– By mechanical, chemical and
physical stimuli or by other
mediators
17. PLATELET ACTIVATING FACTOR
Bioactive phospholipid derived mediator.
Actions:
Aggregate platelets
Bronchoconstriction and Vasoconstriction
Vasodilation and ↑ vascular permeability
↑ leukocyte adhesion
Leukocyte chemotaxis
Stimulation of other mediators particularly
eicosanoids and cytiokines
