Inflammation mediators Flashcards
Characteristics of mediators
-Scavenged or blocked by inhibitors, rapidly decay, and enzymatically destroyed
Two categories of mediators
-Plasma-derived mediators= liver
-Cell-derived mediators
Plasma derived mediators
-Factor XII
-Kinins
-Plasmin
-Complement
-Inflammation inhibitors
Cell-derived mediators
-Vasoactive amines
-Membrane lipid products
-Oxygen metabolites
-Cytokines
-Lysosomal enzyme products
Factor XII
-Start of intrinsic pathway=fibrin
-Activates kinin pathways
-Activate plasminogen
-Activate complement
Kinins
Two pathways: plasma kinin and tissue kinin pathway Product of both is bradykinin
Plasma kinin pathway
Activation of FactorXII and HMWK and prekalilrein complex-> kalikrein cleaves HMWK into bradykinin
Tissue kinin pathway
Stimulated by LMWK cleaved by tissue kallikrien-> kallidin-> bradykinin
Bradykinin activity
-Increased vascular permeability
-Vasodilation
-Extravascular smooth muscle contraction (ie lungs)
-Pain
What inactivates bradykinin
kininases
(angiotensin converting enzyme from endothelium)
Plasmin functions
-Fibrinolysis
-Activation of Factor XII
-Complement activation (cleave C3 to C3a)
Complement
Classical, alternate and MBL pathway and form biologically active products
Complement pathway
Initiated by antibody complexes C1 activated whem IgG crosslink-> C3 convertase-> C3-> C3a and b-> C5 convertase-> C5a and b
Alternate pathway
Activated by bacterial and fungal cell walls, parasites, tumors, and activated plasma proteins. Initiated by C3-> C3 convertase-> C3a and b-> C5 convertase-> C5a and b
MBL pathway
MBL binding to mannose on bacterial surface. All is the same but initiation C3 convertase made by MASP
Terminal pathway
Endpoint of complement activation initiated by C5 to form the MAC and destroy membranes. C5b anchors MAC into lipid membrane so all the other molecules can bind to form MAC. Osmotic lysis of cell
Functions of complement fragments
-C3a and C5a increase vascular permeability
-C3b and C5s neutrophil degranulation
-C3b is an opsonin and enchance platelet aggregation
-C5a and C5b67 are chemotactiv for leukocytes
-C5b6789 lysis cell membrane
Inactivator of complement fragments
-Alpha 2-macroglobulin
-Kininases
-Alpha-1 antitrypsin
Vasoactive amines
Histamine and serotonin (important for rodents) stored in mast cells, basophils, and platelets
What stimulates vasoactive amines
-Allergic reactions
-Cold
-C3a and C5a
-IL1 and IL 8
-Substance P
Biologic effect of vasoactive amines
-Vasodilation (arteriole)
-Increase vascular permeability (venule)
-Smooth muscle constriction (airway)
-Eosinophil chemotaxis
-Pain
-Itching
Arachidonic acid metabolism
Component of cell membrane phospholipids mainly in endothelium, leukocyte, and platelets. Phospholipase A2 results in numerous products
Pathways of arachidonic
COX and LOX
Leukotriene products
-LTB4 chemotaxis, vascular permeability, degranulation of neutrophils
-LTC4 vascular permeability vasoconstriction
-LTC,D,E4 vasodilation and vascular permeability
Lipoxins
Derived from platelets and neutrophils and are pro and anti inflammatory and counteract leukotrienes depending on concentration
Platelet activating factor
Phospholipase A2 and acetyltransferase and do the same thing as the other Arachidonic actions
Reactive oxygen metabolites
Normal products of aerobic metabolism need antioxidants to counter. Produced by leukocytes, endothelium, and pagelets (kill organisms in leukocytes)
Effects of reactive oxygen metabolites
-endothelial injury and increased permeability
-chemotactic substances
-activate cytokines
-AA metabolites
-Inactivate anti inflammatory substances
-Cell and tissue damage
NO metabolies
Produce by endothelium, macrophages and neurons constitutive in endothelium (eNOS) inducible in macrophages (iNOS)
Neuropeptides
Substance P produced by nerves, macrophages, and lymphocytes. Get neurogenic inflammation
Effects of substance P
-Vasodilation
-Vascular permeability
-Leukocyte activation
-Chemotaxis
