Inflammation part 3 Flashcards
Histamine
cell derived
source: mast cells, basophils, platelets
actions: vasodilation, increased vascular permeability, endothelial activaiton
activate in response to injury including trauma, cold, heat, allergic reactions and products of complement called anaphylatoxins.
cause dilation of arterioles and icnreases the permeability of venules. Histamine is considered to be the principal mediator of the immediate transient phase of increased vascular permeability, producing interendothelial gaps in venules, as discussed earlier. Its vasoactive effects are mediated mainly via bidning to receptors, called H1 receptors, on microvascular endothelial cells. The antihistamine drugs that are commonly used to treat some inflammatory reactions, such as allergies, are H1 receptor antagonists that bind to and block the receptor. Histamine also causes contraction of some smooth muscles.
serotonin
cell derived
source: platelets
actions: vasoconstriction
prostaglandins
cell derived
source: mast cells, leukocytes
actions: vasodilation, pain, fever
produced by mast cells, macrophages, endothelial cells, and many other cell types involved in the pathogenesis of pain and fever in inflammation. They are generated by the actions of two cyclooxygenases, called COX1 and COX2. Cox 1 is produced in response to inflammatory stimuli and is also constitutively expressed in most tissues. In contrast, cox 2 is induced by inflammatory stimuli and thus generates the prostaglandins that are involved in inflammatory reactions, but it is low or absent in most normal tissues
leukotrienes
Cell derived
source: mast cells, leukocytes
actions: increased vascular permeability, chemotaxis, leukocyte adhesion and activation
Produced by leukocytes and mast cells. Involved in vascular and smooth muscle reaction and leukocyte recruitment. They are generated by the action of lipoxygenase. LTB4 is a potent chemotactic agentsand activator of neutrophils. LTC4, LTD4, and LTE4 cause intense vasoconstriciton, bronchospasm. (asthma)
platelet activating factor
cell derived
source: leukocytes, mast cells
actions: vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis, degranulation, oxidatve burst
phspholipid mediator (acetyl glycerol ether phospocholine). produced by neutrophils, monocytes, basophils, endothelium, platelets, others
action: platelet sitmulation, vasoconstriciton, bronchoconsriction, vasodilation, increased vascular permeability, leukocyte activation (adhesion, chemotaxis, degranulation, oxidatve burst)
generated from mebrane phosopholipids by actions of phospholipase A2
reactive oxygen species
cell derived
source: leukocytes
action: killing of microbes, tissue damage
nitric oxide
cell derived
source: endothelium, macrophages
actions: vascular smooth muscle releaxating; killing of microbes
cytokines (TNF, Il1, IL6)
Cell derived
leukocytes, activated macrophages
chemotaxis, leukocyte activation
complement
plasma (produced in liver)
leukocyte chemotaxis and activation, direct target killing (MAC), vasodilation (mast cell stimulation)
kinins
plasma (produced in liver)
increased vascular permeability, smooth muscle contraction, vasodilation, pain
bradykinin, vasoactive peptides dervied from plasma proteins kinnogen
it is a vasodilator, increases vascular permeability, bronchial smooth msucle ocntraction, pain.
it is short lived (inactivated by kininases.
cyclooxygenase inhibitors
aspirin and other nonsteroidal antiinflammatory drugs (NSAIDS) such as ibuprofen. They inhibit both COX1 and COX2 and thus inhibit prostaglandin synthesis (hence their efficacy in treating pain and fever); aspirin does this by irreversibly acetylating and inactivating cyclooxygenases.
lipoxygenase inhibitors
5 lipoxygenase is not affected by NSAIDs, and many new inhibitors of this enzyme pathway have been developed. Pharmacologic agents that inhibit leukotriene production are useful in the treatment of asthma.
corticosteroids
broad spectrum antiinflammatory agents taht reduce the transcription of genes encoding COX 2, phosopholipase A2, proinflammatory cytokines (IL1 and TNF), and iNOS.
leukotriene receptor antagnoists
blocks leukotriene receptors and prevent the actions of leukotrienes
vasodilation (eicosanoid)
prostaglandins PGI2 (rpostcyclin), PGE1, PGE2, PGD2
Vasoconstriction (eicosanoid)
Thromboxane A2, leukotrienes C4, D4, E4
INcreased vascular permeability (eicosanoid)
Luekotrienes C4, D4, E4
chemotaxis, leukocyte adhesion (eicosanoid)
leukotrienes B4, HETE
C3a and c5a
increase vascular permeability and cause vasodilation by binding to mast cells and inducing histamine release (anaphylatoxins) thereby increase vascular permeability and cause vasodilation. They are called anaphylatoxins because they have effects similar to those of mast cell mediators that are involve din the reaction called anaphylaxis
c5a
chemotactic for neutrophils, monocytes, eosinophils, and basophils. increases adhesivness o fneutrophils to endothelium. Stimualtes synthesis and secretion of arachidonic acid metabolites
C3b and Ic3b
opsonization and phagocytosis: binds to microbial surface and promotes phagocytosis.
hagman factor
it is a protein syntehsized by the liver
called clotting factor XII (inactive form)
provides additional source of vasoactive mediators
activated by negatively charged surfaces, bacterial LPS, sodium urate crystals and enzymes (trypsin and plasmain)
