Download chemical mediators of inflammation

CHEMICAL MEDIATORS OF
INFLAMMATION
2 GROUPS
1.MEDIATORS RELEASED BY CELLS
2.MEDIATORS DERIVED FROM PLASMA.
CHEMICAL MEDIATORS OF
INFLAMMATION
CELL DERIVED MEDIATORS
1.VASOACTIVE AMINES-HISTAMINE AND
SEROTONIN
HISTAMINE
PRESENT IN GRANULES OF MAST CELLS,
BASOPHILS AND PLATELETS.
VARIOUS AGENTS WHICH RELEASE
HISTAMINE FROM THESE CELLS ARE
HISTAMINE
A.STIMULI LIKE HEAT , COLD ,
IRRADIATION,TRAUMA,IRRITANT
CHEMICALS,IMMUNOLOGICAL
REACTIONS.
HISTAMINE
B.ANAPHYLATOXINS-COMPLIMENT
FRAGMENTS-C3a ,C5a
C.HISTAMINE RELEASING FACTORS FROM
NEUTROPHILS,MONOCYTES,
PLATELETS
HISTAMINE
D. NEUROPEPTIDES-SUBSTANCE
P
E. INTERLEUKINS
HISTAMINE
ACTION OF HISTAMINEVASODILATATION,
INCREASED VASCULAR PERMEABILITY,
ITCHING AND PAIN
VASOACTIVE AMINES SEROTONIN(5HT)
VASOACTIVE AMINES SEROTONIN(5HT)PRESENT IN
CHROMAFFIN CELLS OF GIT,SPLEEN,
NERVOUS TISSUE,
MAST CELLS AND PLATELETS
VASOACTIVE AMINES SEROTONIN(5HT)
ACTION IS SIMILAR TO HISTAMINE
BUT IT IS LESS POTENT MEDIATOR OF
INCREASED VASCULAR PERMEABILITY AND
VASODILATATION
2.ARACHIDONIC ACID
METABOLITES(EICOSANOIDS)
2 PATHWAYS OF ACTIVASION1.CYCLOOXYGENASE PATHWAY
AND
2.LIPO-OXYGENASE PATHWAY
EICOSANOIDS
METABOLITES OF CYCLO-OXYGENASE(A FATTY ACID ENZYME)
PATHWAY
PROSTAGLANDINS,
THROMBOXANE A2 &
PROSTACYCLIN.
1.PROSTAGLNDINSPGD2,PGE2, PGF2α
EICOSANOIDS
METABOLITES OF CYCLO-OXYGENASE(A FATTY ACID ENZYME)
PATHWAY
PGD2 AND PGE2-CAUSE
INCREASED VENULAR PERMEABILITY,
VASODILATATION,
BRONCHODILATATION,
INHIBIT INFLAMMATORY CELL FUNCTION
ARACHIDONIC ACID METABOLITES
METABOLITES
OF LIPO-OXYGENASE PATHWAY
LIPO-OXYGENASE ENZYME ACT ON
ACTIVATED ARACHIDONIC ACID TO FORM
HYDROPEROXY COMPOUND,
5-HPETE WHICH ON FURTHER PEROXYDATION
FORMS 2 METABOLITES
ARACHIDONIC ACID METABOLITES
METABOLITES OF LIPO-OXYGENASE
PATHWAY
A.5HETE - CHEMOTACTIC AGENT FOR
NEUTROPHILS
B.LEUKOTRIENS OR SLOW REACTING
SUBSTANCES OF ANAPHYLAXIS-
METABOLITES OF LIPO-OXYGENASE
PATHWAY
LTA4 - UNSTABLE
LTB4 - CHEMOTACTIC FOR
PHAGOCYTES
METABOLITES OF LIPO-OXYGENASE
PATHWAY
LTC4 , LTD4 , LTE4VASOCONSTRICTION,
BRONCHOCONSTRICTION,
INCREASED VASCULAR PERMEABILITY
3.LYSOSOMAL COMPONENTS
INFLAMMATORY CELLS -NEUTROPHILS AND
MONOCYTES CONTAIN LYSOSOMAL
GRANULES WHICH RELEASE A VARIETY OF
MEDIATORS OF INFLAMMATION
3.LYSOSOMAL COMPONENTS
GRANULES OF NEUTROPHILS
A.SPECIFIC OR SECONDARY-CONTAIN
LACTOFERRIN,LYSOZYME,
ALKALINE PHOSPHATASE, COLLAGENASE
3.LYSOSOMAL COMPONENTS
B.LARGE PRIMARY GRANULES AZUROPHIL GRANULES HAVE
MYELOPEROXIDASE,
ACID HYDROLASES WHICH DESTROY
PHAGOLYSOSOMAL CONTENT
3.LYSOSOMAL COMPONENTS
NEUTRAL PROTEASES SUCH AS
ELASTASE,COLLAGENASE AND PROTEINASE
WHICH ATTACK EXTRACELLULAR
CONSTITUENTS SUCH AS BASEMENT
MEMBRANE,COLLAGEN,
ELASTIN,CARTILAGE
3.LYSOSOMAL COMPONENTS
GRANULES OF MONOCYTES AND TISSUE
MACROPHAGES RELEASE
ACID PROTEASES,
COLLAGENASES,
3.LYSOSOMAL COMPONENTS
ELASTASE AND
PLASMINOGEN ACTIVATOR.
THEY ARE MORE ACTIVE IN CHRONIC
INFLAMMATION
4.PLATELET ACTIVATING FACTOR(PAF)
RELEASED FROM IgE SENSITISED BASOPHILS
OR MAST CELLS,OTHER
LEUKOCYTES,ENDOTHELIAL CELLS,AND
PLATELETS.CAUSE
PLATELET AGGREGATION AND RELEASE
REACTION,
4.PLATELET ACTIVATING FACTOR(PAF)
INCREASED VASCULAR
PERMEABILITY,
VASOCONSTRICTION,
VASODILATATION IN LOW
CONCENTRATION,
BRONCHOCONSTRICTION,
4.PLATELET ACTIVATING FACTOR(PAF)
ADHESION OF LEUKOCYTES TO
ENDOTHELIUM,
CHEMOTAXIS
5.CYTOKINES
POLYPEPTIDES PRODUCED BY ACTIVATED
LYMPHOCYTES(LYMPHOKINES) AND
ACTIVATED MONOCYTES(MONOKINES).
HAVE AUTOCRINE OR PARACRINE ACTION
5.CYTOKINES(CHEMOKINES)
IL-1 AND TNF α FROM ACTIVATED
MACROPHAGES,
TNF-β AND IF GAMA PRODUCED BY
ACTIVATED T CELLS
CHEMOKINES INCLUDEIL8 AND PF4
ACTION OF CYTOKINES
l. IL-1,TNFα,TNFβ –
CAUSE
LEUKOCYTE ADHESION,
THROMBOGENICITY,
FIBROBLAST PROLIFERATION,
ACUTE PHASE REACTIONS
ACTION OF CYTOKINES
ll. IF GAMA - ACTIVATION OF
MACROPHAGES,NEUTROPHILS,
SYNTHESIS OF NITRIC OXIDE
ACTION OF CYTOKINES
iii. CHEMOKINES
CHEMOKINESARE A FAMILY OF CHEMOATTRACTANTS
FOR INFLAMMATORY CELLS
1. IL-8 CHEMOTACTIC FOR NEUTROPHILS
ACTION OF CYTOKINES
2. PLATELET FACTOR 4 - CHEMOTACTIC
FOR NEUTROPHILS,MONOCYTES AND
EOSINOPHILS
3.MCP-1- FOR MONOCYTES
4.EOTAXIN- CHEMOTACTIC FOR
EOSINOPHILS
6.NITRIC OXIDE AND OXYGEN
METABOLITES
NO - PRODUCED BY ENDOTHELIAL CELLS AND
ACTIVATED MACROPHAGES
ACTIONS
VASODILATATION,
ANTIPLATELET ACTIVATING AGENT
MICROBICIDAL ACTION
7.OXYGEN DERIVED METABOLITES
FROM ACTIVATED NEUTROPHILS AND
MACROPHAGES
OXYGEN DERIVED FREE RADICALS
HAVE FOLLOWING ACTION IN
INFLAMMATION
a. ENDOTHELIAL CELL DAMAGE- INCREASED
PERMEABILITY
OXYGEN METABOLITES
b. ACTIVATION OF PROTEASE AND
INACTIVATION OF ANTIPROTEASETISSUE MATRIX DAMAGE,DAMAGE TO OTHER
CELLS
FREE RADICALS ARE COUNTERACTED BY
ANTIOXIDANTS
ANTIOXIDANTS
ARE ENDOGENOUS & EXOGENOUS
SUBSTANCES WHICH INACTIVATES FREE
RADICALS-
ANTIOXIDANTS
1.VITAMINS E,A, C
2.SULFHYDRIL CONTAINING COMPOUNDSCYSTEIN,GLUTATHIONE
3 SERUM PROTEINS-CERULOPLASMIN &
TRANSFERRIN
11 .PLASMA DERIVED MEDIATORS
PLASMA PROTEASES
PRODUCED BY ACTIVATION AND
INTERACTION OF 4 INTERLINKED SYSTEM
KININ, CLOTTING, FIBRINOLYTIC AND
COMPLIMENT SYSTEM
PLASMA DERIVED MEDIATORS
PLASMA PROTEASES
HAGEMAN FACTOR(F-XII)-ACTIVATED BY
CONTACT WITH BASEMENT MEMBRANE AND
BACTERIAL ENDOTOXINS IN VIVO LEADS TO
PLASMA DERIVED MEDIATORS
PLASMA PROTEASES
ACTIVATION OF CLOTTING, FIBRINOLYTIC,
AND KININ SYSTEMEND PRODUCTS OF ACTIVATION OF THESE
SYSTEMS GENERATE PERMEABILITY FACTORS
WHICH FURTHER ACTIVATE CLOTTING
SYSTEM
COAGULATION SYSTEM
1.THE KININ SYSTEM
ON ACTIVATION BY FACTOR XIIa-GENERATES
BRADYKININ WHICH CAUSESMOOTH MUSCLE CONTRACTION,
VASODILATATION,
INCREASED VASCULAR PERMEABILITY AND
PAIN
2.THE FIBRINOLYTIC SYSTEM
ACTIVATED BY PLASMINOGEN
ACTIVATERCONVERTS PLASMINOGEN TO PLASMIN
2.THE FIBRINOLYTIC SYSTEM
ACTIONS OF PLASMIN
DEGRADES FIBRIN TO FIBRIN SPLIT PRODUCTS
WHICH INCREASE VASCULAR
PERMEABILITY,CHEMOTAXIS TO LEUKOCYTES
3.THE CLOTTING SYSTEM
ACTIVATED BY XIIa- RELEASE FIBRIN AND
FIBRINOPEPTIDESWHICH CAUSE
INCREASED VASCULAR PERMEABILITY,
CHEMOTAXIS,
ANTICOAGULANT ACTIVITY
4.THE COMPLEMENT SYSTEM
ACTIVATION OF COMPLEMENT PATHWAYS
RELEASE ANAPHYLATOXINS-C3a,C4a,C5a
- MAST CELLS TO RELEASE VASOACTIVE
AMINES
THE COMPLEMENT SYSTEM
ACTIONS OF ANAPHYLATOXINS RELEASE OF HISTAMINES FROM MAST CELLS
AND BASOPHILS - CAUSE
INCREASED VASCULAR PERMEABILITYOEDEMA
THE COMPLEMENT SYSTEM
C3b AUGMENTS PHAGOCYTOSIS
C5a-CHEMOTACTIC FOR LEUKOCYTES
2. MAC–MEMBRANE ATTACK COMPLEX CAUSES PORES IN THE CELL MEMBRANE OF
MICROORGANISMS
ROLE OF MEDIATORS IN DIFFERENT
REACTION OF INFLAMMATION
ROLE OF INFLAMMATION
MEDIATORS
VASODILATATION
PROSTAGLANDINS,NITRIC
OXIDE,HISTAMINE
INCREASED VASCULAR
PERMEABILITY
HISTAMINE AND
SEROTONIN,C3a AND C5a(BY
LIBERATING VASOACTIVE
AMINES FROM MAST CELLS
AND OTHER
CELLS),BRADYKININ,LEUKOTRI
ENES C 4, D 4, E 4 ,PAF,
SUBSTANCE P
CHEMOTAXIX ,LEUKOCYTE
RECRUITMENT AND
ACTIVATION
TNF,IL1,CHEMOKINES,C3a,C5a
,LEUKOTRIENEB 4 ,BACTERIAL
PRODUCTS LIKE NFORMYLMETHYL PEPTIDES
FEVER
IL1 ,TNF, PROSTAGLANDINS
PAIN
PROSTAGLANDINS,BRADYKININ