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Questions and Answers
What triggers the rapid degranulation of mast cells?
What triggers the rapid degranulation of mast cells?
What is the primary function of serotonin in the body?
What is the primary function of serotonin in the body?
Which receptors do antihistamine drugs primarily target?
Which receptors do antihistamine drugs primarily target?
What mediates the vasoactive effects of histamine?
What mediates the vasoactive effects of histamine?
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What process releases arachidonic acid from membrane phospholipids?
What process releases arachidonic acid from membrane phospholipids?
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Which of the following best describes the role of leukotrienes in inflammation?
Which of the following best describes the role of leukotrienes in inflammation?
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In humans, where is serotonin primarily found as a mediator?
In humans, where is serotonin primarily found as a mediator?
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What role does histamine play in relation to venules in inflammation?
What role does histamine play in relation to venules in inflammation?
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Which of the following best describes the nature of mediators of inflammation?
Which of the following best describes the nature of mediators of inflammation?
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What process allows for the rapid secretion of stored mediators from cells during inflammation?
What process allows for the rapid secretion of stored mediators from cells during inflammation?
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How are plasma-derived mediators primarily activated?
How are plasma-derived mediators primarily activated?
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What role does the mediator TNF play in inflammation?
What role does the mediator TNF play in inflammation?
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Which of the following statements about the short-lived nature of most mediators is true?
Which of the following statements about the short-lived nature of most mediators is true?
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What is a primary function of vasoactive amines like histamine during inflammation?
What is a primary function of vasoactive amines like histamine during inflammation?
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Which statement about the action of primary mediators is correct?
Which statement about the action of primary mediators is correct?
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What is the role of complement activation products in inflammation?
What is the role of complement activation products in inflammation?
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What triggers the activation of phospholipase A2?
What triggers the activation of phospholipase A2?
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Which enzyme is responsible for generating prostaglandins?
Which enzyme is responsible for generating prostaglandins?
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Which statement about COX2 is true?
Which statement about COX2 is true?
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What is the primary function of prostacyclin (PGI2)?
What is the primary function of prostacyclin (PGI2)?
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Which eicosanoid is primarily produced by platelets?
Which eicosanoid is primarily produced by platelets?
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Which of the following is NOT involved in mediating inflammation?
Which of the following is NOT involved in mediating inflammation?
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Which prostaglandin is considered to be important in inflammatory reactions?
Which prostaglandin is considered to be important in inflammatory reactions?
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What distinguishes COX1 from COX2?
What distinguishes COX1 from COX2?
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What is the main role of PGD2 in inflammation?
What is the main role of PGD2 in inflammation?
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Which type of leukotriene is primarily responsible for causing bronchospasm?
Which type of leukotriene is primarily responsible for causing bronchospasm?
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How do lipoxins differ from prostaglandins and leukotrienes?
How do lipoxins differ from prostaglandins and leukotrienes?
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What is the function of LTB4 in the inflammation response?
What is the function of LTB4 in the inflammation response?
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Which of the following statements is true regarding leukotrienes?
Which of the following statements is true regarding leukotrienes?
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What triggers the production of leukotrienes in leukocytes and mast cells?
What triggers the production of leukotrienes in leukocytes and mast cells?
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Which enzyme is primarily responsible for leukotriene synthesis in neutrophils?
Which enzyme is primarily responsible for leukotriene synthesis in neutrophils?
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What effect does PGF2a have in the body?
What effect does PGF2a have in the body?
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Study Notes
Mediators of Inflammation
- Mediators of inflammation are substances that initiate and regulate inflammatory reactions.
- They are either secreted by cells or generated from plasma proteins.
- Cell-derived mediators are stored in intracellular granules and released by exocytosis or synthesized de novo.
- Plasma-derived mediators are produced in the liver and are present in the circulation as inactive precursors that are activated by proteolytic cleavages.
- Active mediators are produced in response to stimuli such as microbial products and substances from necrotic cells.
- Most mediators are short-lived and are inactivated by enzymes or scavenged.
- One mediator can stimulate the release of other mediators, creating a cascade of effects.
Vasoactive Amines: Histamine and Serotonin
- Histamine is a vasoactive amine stored in mast cells, basophils, and platelets.
- It is released by degranulation triggered by various stimuli:
- Physical injury
- Antibody binding to mast cells
- Complement products (anaphylatoxins)
- Neuropeptides
- Cytokines
- It causes dilation of arterioles and increases venule permeability, leading to edema.
- Its vascular effects are mediated by binding to H1 receptors.
- Histamine also causes contraction of some smooth muscles.
- Serotonin is a vasoactive mediator present in platelets, neuroendocrine cells, and mast cells in rodents (but not humans).
- It is mainly a neurotransmitter in the gastrointestinal tract.
- Its vasoconstrictor function in inflammation is unclear.
Arachidonic Acid Metabolites
- Prostaglandins and leukotrienes are lipid mediators produced from arachidonic acid (AA) present in membrane phospholipids.
- AA is a 20-carbon polyunsaturated fatty acid released from membrane phospholipids by phospholipase A2.
- Eicosanoids (AA-derived mediators) are synthesized by two major enzyme classes:
- Cyclooxygenases (COX)
- Lipoxygenases
- They bind to G-protein coupled receptors on various cell types and mediate virtually every step of inflammation.
Prostaglandins
- Prostaglandins are produced by mast cells, macrophages, endothelial cells, and other cell types.
- They are involved in the vascular and systemic reactions of inflammation.
- COX1 is constitutively expressed and serves a homeostatic function in various tissues.
- COX2 is induced by inflammatory stimuli and generates prostaglandins involved in inflammatory reactions.
- Prostaglandins are classified into series based on their structure (e.g., PGD, PGE, PGF, PGG, PGH).
- The most important ones in inflammation:
- PGE2
- PGD2
- PGF2a
- PGI2 (prostacyclin)
- TxA2 (thromboxane A2)
- Each prostaglandin is derived by the action of a specific enzyme on an intermediate in the pathway.
- TxA2 is a potent platelet aggregator and vasoconstrictor.
- Prostacyclin (PGI2) is a vasodilator, inhibitor of platelet aggregation, and potentiates the permeability-increasing and chemotactic effects of other mediators.
- A thromboxane-prostacyclin imbalance has been implicated in thrombosis.
- PGD2 and PGE2 cause vasodilation and increase postcapillary venule permeability, contributing to edema.
- PGF2a stimulates smooth muscle contraction and small arteriole constriction.
- PGD2 is a chemoattractant for neutrophils.
- Prostaglandins are involved in the pathogenesis of pain and fever in inflammation.
Leukotrienes
- Leukotrienes are produced by leukocytes and mast cells by the action of lipoxygenases.
- 5-lipoxygenase is the predominant form in neutrophils.
- It converts AA to 5-hydroxyeicosatetraenoic acid, a chemoattractant for neutrophils.
- LTB4 is a potent chemotactic agent and activator of neutrophils, promoting aggregation, adhesion, ROS generation, and lysosomal enzyme release.
- Cysteinyl-containing leukotrienes (LTC4, LTD4, LTE4) cause intense vasoconstriction, bronchospasm, and increased venule permeability.
- They are more potent than histamine in increasing vascular permeability and causing bronchospasm.
Lipoxins
- Lipoxins are also generated from AA by the lipoxygenase pathway.
- Unlike prostaglandins and leukotrienes, lipoxins suppress inflammation.
- They inhibit neutrophil chemotaxis and adhesion to endothelium.
- Their biosynthesis requires two cell populations: leukocytes (neutrophils) produce intermediates, and platelets convert them into lipoxins.
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Description
This quiz explores the various mediators of inflammation, including both cell-derived and plasma-derived substances. It covers how these mediators function, their activation, and their roles in inflammatory responses, with a focus on vasoactive amines like histamine and serotonin.
