Chemical Mediators of Inflammation Flashcards
Examples of etiological processes that might incite an inflammatory process.
Neoplastic process OR Non-Neoplastic: bugs, dead tissue, foreign material, immune complexes
Discuss the role that inflammatory mediators play in cell-to-cell communication.
Most signaling is receptor mediated:
Local effects: Autocrine signaling (self-stimulating) or Paracrine (local cell stimulating)
Systemic effects: endocrine-like, signals travel through vasculature to remote organs, e.g. brain, liver, bone marrow.
Vasoactive amines
Histamine
Source: Mast cells, Basophils, Platelets
Actions: Vasodilation, increase vascular permeability, Contract bronchial smooth muscle
Nature: Preformed
Serotonin
Source: Platelets
Actions: Increase vascular permeability
Nature: Pre-formed
Prostaglandins
Source: Mast cells, Platelets, Macrophages, lymphocytes, PMNS, endothelial cells
Actions: Vasodilation (PGI2), platelet ag. & act., constrict bronchial smooth muscle, fever, pain
Nature: Synthesized on demand
Leukotrienes
Source: mast cells, basophils, macrophages, lymphocytes, PMNs
Actions: Increase vascular permeability, constrict bronchial smooth muscle
Nature: Synthesized on demand
Thromboxane
Source: Platelets
Actions: Vasoconstriction, Platelet Ag. & Act.
Nature: Synthesized on demand.
Platelet Activating Factor
Source:Mast cells, basophils, platelets, macrophages, PMNs, endothelial cells
Actions: Vasodilation at low conc., vasoconstriction, increase vascular permeability at low conc., WBC chemotaxis/recruit/activ., platelet ag. & act, bronchial smooth muscle constriction
Reactive oxygen species
Source: Macrophages, lymphocytes, PMNs
Actions: Tissue/Microbe damage
Nature: Synthesized on demand
Nitric Oxide (NO)
Source: Macrophages (iNOS), endothelial cells (eNOS) neural parenchyma (nNOS)
Actions: Vasodilation/relaxation of smooth muscle (e,i,n); chemotaxis of wbc (i), reduced leukocyte adhesion, platelet adhesion (e), collateral damage to tissue (i) neurotransmitter release (n)
Nature: synthesized on demand
TNF
Source: Mast cells, basophils, macrophages, lymphocytes
Actions: WBC chemotaxis/recruit/activ., calor
Nature: synthesized on demand
Interleukins
Source: macrophages, endothelial cells
Actions: WBC chemotaxis/recruit/activ., calor
Nature: synthesized on demand
Interferons
Source: multiple
Actions: Interfere with viral replicaiton
Nautre: synthesized on demand
Chemokines
Source: Mast cells, basophils, macrophages, lymphocytes, endothelial cells
Actions: WBC chemotaxis
Nature: synthesized on demand
Cytoplasmic Granule Content
Source: Macrophages, PMNs
Actions: WBC chemotaxis, tissue/microbe damage
Nature: Preformed
Substance P
Source: Nerve fibers
Actions: Increase vascular permeablility, Pain
Nature: Preformed
Thrombin
Source: Liver
Actions: WBC chemotaxis
Plasmin
Source: Liver
Actions: Vasodilation
Complement system: C3a, C5a
Source: Liver
Actions: Vasodilation (mast cell stim.), Increase vascular permeability (mast cell stim.), tissue /microbe damage (Membrane attack complex)
Bradykinin
Source: Liver
Actions: Vasodilation
Activation of Factor XII
Factor XII can be activated by:
A) vascular permeability increase (exposure to extracellular collagen)
B) Endothelial cell damage: (exposure to collagen/basement membrane)
C) Activated platelets
Activation of Factor XII—> becomes Factor XIIa
Activation of Thrombin
Thrombin (a protease) binds to platelets, endothelial cells, smooth muscle receptors: protease activated receptors (PARS)—> P-selectin mobilized–> endothelial adhesion stimulated–> promotes formation of prostaglandins, PAF, NO, cytokines
Kallikrein Pathway
Pre-kallikrein converted to Kallikrein protease–> (Bradykinin formed from HMWK)–> Activates C5 to C5a (anaphylatoxin)
ALSO
Kallikrein cleaves Plasminogen–> Plasmin
a) cleaves fibrin to form fibrin degradation products, increases vascular permeability
b)Activations C3 to C3a (anaphylatoxin)
