L6 Flashcards
CHEMICAL MEDIATORS OF INFLAMMATION?
Def. : Chemical substances released from the cells, the plasma, or damaged tissue itself.
Co-ordinate the development of the inflammatory response.
Chemical mediators, They are broadly classified into 2 groups:
i) mediators released by cells; and
ii) mediators originating from plasma.
The inflammatory response
6
1-Vasoconstriction
2-Vasodilation
3-Increased vascular permeability
4-Emigration, chemotaxis
5-Phagocytosis
6-Tissue destruction
Properties of chemical mediators
o Active mediators are produced in response to various stimuli
o Most of chemical mediators can stimulate the release of other mediators.
o Amplify and maintain the inflammatory response o Most of these are short lived
o Releasing stimuli:
• Direct physical , chemical or mechanical injury
• Microbes or their toxins
• ECM fragments
• Fragments of complement system e.g C3a and C5a
• Thrombin for most of cellular mediators
• Immune complexes
• Binding of IgE- Ag- complexes (for vasoactive amines)
• Cytokines (IL-1, IL-8 for vasoactive amines), (TNF, IFNγ for free radicals )
• TXA2, ADP for PAF
o Mechanism of action:
– Receptor-ligand interactions
– Direct enzymatic activity
– Mediate oxidative damage
Chemical mediators released by cells ? 6
I-VASOACTIVE AMINES**: 1-Histamine 2- Serotonin 3- Neuropeptides
II-ARACHIDONIC ACID METABOLITES via 1- cyclo-oxygenase pathway (prostaglandins, thromboxane A2, prostacyclin) 2- lipo-oxygenase pathway (5-HETE,leukotrienes, lipoxins)
III-Platelet activating factor
IV-Cytokines (IL-1, TNF-α, TNF-β, IFN-γ, chemokines)
V-Lysosomal components** (from PMNs, macrophages)
VI-Free radicals (Oxygen metabolites, nitric oxide)
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