Cell Derived Mediators of Inflammation Flashcards
What are types of cell-derived mediators of inflammation?
Vasoactive amines
Arachidonic acid metabolites
Nitric oxide
Platelet activating factor
Cytokines
What cells produce histamine?
Basophils and mast cells
What is the function of histamine?
Increased vascular permeability and increased vasodilation
What is the function of serotonin as an inflammatory mediator?
Platelet activation
What are two cell-derived vasoactive amines that mediate inflammation?
Histamine and serotonin
What is the most important “superstar” cell-derived mediator of inflammation?
Histamine
Where are the highest levels of serotonin located in the body?
Gut
Where is arachidonic acid located?
Cell membrane
What enzyme releases arachidonic acid from the cell membrane?
Phospholipase
What plasma derived mediator of inflammation produced from the complement system assists in arachidonic acid metabolism?
C5a
What enzyme converts arachidonic acid into leukotrienes and lipoxins?
Lipoxygenase (LOX)
What are examples of leukotrienes?
LTB4
LTC4
LTD4
LTE4
What is the function of LTB4?
- chemotactic agent for phagocytic cells
- stimulates phagocytic cell adherence
- increases vascular permeability
What is the difference between C5a and LTB4 as chemotactic agents?
C5a is a plasma derived chemotactic agent in the complement system while LTB4 is a cell derived chemotactic agent for phagocytes in the LOX pathway
What is the function of LTC4, LTD4, and LTE4?
- Bronchoconstriction (smooth muscle contraction)
- increased vasodilation and vascular permeability
What leukotrienes are present in asthmatic and type I hypersensitivity reactions?
LTB4, LTC4, LTD4, and LTE4
What drug can inhibit the lipoxygenase enzyme and the conversion of arachidonic acid to leukotrienes?
Singulair (or other anti-asthmatics)
What enzyme converts arachidonic acid to prostaglandins and thromboxane?
Cyclooxygenase (COX)
What is the function of PGE2 and PGD2?
- Vasodilation
- increased vascular permeability
What is the function of PGI2?
Inhibits platelet aggregation
(AKA prostacyclin -> keeps the blood cyclin’)
What is PGI2 called?
Prostacyclin
What is TXA2?
Thromboxane
What is the function of TXA2?
- Vasoconstriction
- increases platelet aggregation
What drugs can inhibit the cyclooxygenase (COX) enzyme?
NSAIDS such as Vioxx, Celebrex, naproxen, ibuprofen, indomethacin, and aspirin
What does fish oil inhibit in the arachidonic acid cascade?
Blockage of linoleic acid conversion to arachidonic acid and blocks arachidonic acid release from the cell membrane
What induces the systemic acute-phase reaction?
Cytokines
What are the various roles of cytokines in inflammation?
- Synthesis of endothelium adhesion molecules and nitric oxide
- Induce aggregation of neutrophils
- induce systemic acute-phase reactions
What endothelium adhesion molecules are synthesized as a result of cytokines?
LTB4, thrombin, selectins, integrins
What is the systemic acute-phase reaction?
- Feeling of being sick due to cytokines activation by macrophages
- Fever, decreased appetite, increased protein synthesis, leukocytosis
What can stimulate cytokine secretion by macrophages and T lymphocytes?
Endotoxins, immune complexes from a type III hypersensitivity reaction, and physical injury
What white blood cells release cytokines?
Macrophages and T lymphocytes
What are examples of cell-derived cytokines that mediate inflammation?
IL-1, IL-2, IL-6, IL-8, TNF
What is interleukin 1 (IL-1) and what is its function?
- Cytokine known as an “endogenous pyrogen” that is the primary cause of fever
- Primes WBC for inflammation by increasing adherence and metabolism
What is the function of tumor necrosis factor (TNF)?
Triggers cell death
What cytokine does tumor necrosis factor (TNF) often get released with?
Interleukin 1 (IL-1)
What is interleukin 2 (IL-2) and what is its function?
Cytokine involved in “self tolerance” that trains cells to know the difference between “self” and “non-self”
What is interleukin 6 (IL-6) and what is its function?
Cytokine involved in the secondary fever response; Implicated in schizophrenia
What is interleukin 8 (IL-8) and what is its function?
Cytokine that functions as a cell-derived chemotactic agent for neutrophils
What cells synthesize nitric oxide?
Endothelial cells and macrophages
What is the function of nitric oxide?
Vasodilation and cytotoxic as a peroxynitrite free radical
What is the function of interferons?
- leukocyte activation
- interfere w/ viral replication
What is platelet activating factor (PAF)?
- very potent & versatile mediator
- derived from membrane phospholipids
- synthesized by all inflammatory cells, endothelial cells, & injured tissue
What are the functions of PAF?
- increase permeability
- vasodilation
- platelet aggregation
- increase arachidonic acid metabolism
- increase leukocyte adherence
