Lecture # 26
ACUTE INFLAMMATION-3
Dr. Iram Sohail
Assistant Professor
Pathology
College Of Medicine
OBJECTIVES
• Chemical mediators of inflammation
– Cell derived mediators
– Plasma protein derived mediators
CHEMIAL MEDITORS OF INFLAMMATION
• Chemical mediators are substances which are
responsible for the events of inflammation.
• They may be produced locally at the site of
inflammation or synthesized in liver and then
secreted in circulation.
There are 2 types of mediators
• Cell derived mediators
• Plasma protein derived mediators
CELL DERIVED MEDIATORS
They are produced by
• Mast cells
• Endothelial cells
• Tissue macrophages
• WBCs
Cell derived mediators are
• Histamine
• Serotonin
• Prostaglandins (PG)
• Leukotrienes
• Platelet activating factor (PAF)
• Reactive oxygen species
• Nitric oxide
• Cytokines
• Neuropeptides
• These are different cell derived mediators and
their sources.
• Different actions of cell derived mediators of
inflammation
Mediator
Source
Principal Actions
Histamine
Mast cells, basophils, platelets
Vasodilation, increased vascular
permeability, endothelial
activation
Serotonin
Platelets
Vasodilation, increased vascular
permeability
Prostaglandins
Mast cells, leukocytes
Vasodilation, pain, fever
Leukotrienes
Mast cells, leukocytes
Increased vascular permeability,
chemotaxis, leukocyte adhesion
and activation
Cell-Derived
Platelet-activating factor
Leukocytes, endothelial cells
Vasodilation, increased vascular
permeability, leukocyte
adhesion, chemotaxis,
degranulation, oxidative burst
Reactive oxygen species
Leukocytes
Killing of microbes, tissue
damage
Nitric oxide
Endothelium, macrophages
Vascular smooth muscle
relaxation; killing of microbes
Cytokines (e.g. TNF, IL-1)
Macrophages, lymphocytes,
endothelial cells, mast cells
Local endothelial activation
(expression of adhesion
molecules), systemic acutephase response; in severe
infections, septic shock
Chemokines
Leukocytes, activated
macrophages
Chemotaxis, leukocyte
activation
• Arachidonic acid metabolites (PG & LTs)
formation and their roles in inflammation
• Principle inflammatory actions of Arachidonic
acid metabolites
Action
Eicosanoid
Vasodilation
PGI2 (prostacyclin), PGE1, PGE2, PGD2
Vasoconstriction
Thromboxane A2, leukotrienes C4, D4, E4
Increased vascular permeability
Leukotrienes C4, D4, E4
Chemotaxis, leukocyte adhesion
Leukotriene B4
Major cytokines in the acute inflammation are
• Tumor necrosis factor
(TNF)
&
• Interleukin-1 (IL-1)
PLASMA PROTEIN DERIVED MEDIATORS
• Plasma protein derived mediators are involved
in many inflammatory reactions.
Plasma protein mediators are
A. Complements
B. Coagulation & kinin system
A. Complements
• Complement system is composed of plasma
proteins and plays an important role in events
of inflammation.
In plasma these complements are present in
inactive form.
• They activated by 2 pathways
i.
Classical pathway
ii. Lectin pathway
The main complements are
1. C3a, C5a
• Causes
– increased vascular permeability & vasodilation
– also called anaphylotoxins
2. C5a
• Causes
– Leukocytes activation, adhesion & Chemotaxis
3. C3b
• Causes
– Opsonization & phagocytosis
B. Coagulation & kinin system
• Summary of cell derived & plasma protein
mediators of inflammation