Chemical Mediators of Inflammation

Question 1

Examples of etiological processes that might incite an inflammatory process.

Answer 1

Neoplastic process OR Non-Neoplastic: bugs, dead tissue, foreign material, immune complexes

Question 2

Discuss the role that inflammatory mediators play in cell-to-cell communication.

Answer 2

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.

Question 3

Vasoactive amines

Answer 3

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

Question 4

Prostaglandins

Answer 4

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

Question 5

Leukotrienes

Answer 5

Source: mast cells, basophils, macrophages, lymphocytes, PMNs
Actions: Increase vascular permeability, constrict bronchial smooth muscle
Nature: Synthesized on demand

Question 6

Thromboxane

Answer 6

Source: Platelets
Actions: Vasoconstriction, Platelet Ag. & Act.
Nature: Synthesized on demand.

Question 7

Platelet Activating Factor

Answer 7

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

Question 8

Reactive oxygen species

Answer 8

Source: Macrophages, lymphocytes, PMNs
Actions: Tissue/Microbe damage
Nature: Synthesized on demand

Question 9

Nitric Oxide (NO)

Answer 9

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

Question 10

TNF

Answer 10

Source: Mast cells, basophils, macrophages, lymphocytes
Actions: WBC chemotaxis/recruit/activ., calor
Nature: synthesized on demand

Question 11

Interleukins

Answer 11

Source: macrophages, endothelial cells
Actions: WBC chemotaxis/recruit/activ., calor
Nature: synthesized on demand

Question 12

Interferons

Answer 12

Source: multiple
Actions: Interfere with viral replicaiton
Nautre: synthesized on demand

Question 13

Chemokines

Answer 13

Source: Mast cells, basophils, macrophages, lymphocytes, endothelial cells
Actions: WBC chemotaxis
Nature: synthesized on demand

Question 14

Cytoplasmic Granule Content

Answer 14

Source: Macrophages, PMNs
Actions: WBC chemotaxis, tissue/microbe damage
Nature: Preformed

Question 15

Substance P

Answer 15

Source: Nerve fibers
Actions: Increase vascular permeablility, Pain
Nature: Preformed

Question 16

Thrombin

Answer 16

Source: Liver
Actions: WBC chemotaxis

Question 17

Plasmin

Answer 17

Source: Liver
Actions: Vasodilation

Question 18

Complement system: C3a, C5a

Answer 18

Source: Liver
Actions: Vasodilation (mast cell stim.), Increase vascular permeability (mast cell stim.), tissue /microbe damage (Membrane attack complex)

Question 19

Bradykinin

Answer 19

Source: Liver
Actions: Vasodilation

Question 20

Activation of Factor XII

Answer 20

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

Question 21

Activation of Thrombin

Answer 21

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

Question 22

Kallikrein Pathway

Answer 22

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)