Chemical Mediators of Inflammation I Flashcards
What cells make ROS?
all leukocytes
What is the problem with ROS?
they’re nonspecific- collateral damage
What are the functions of chemokines?
chemotaxis, migration of inflammatory cells
What is a basophil called when it enters the tissue?
a mast cell
Why are mediators short lived?
b/c of decay, inactivation, inhibition, scavenging
Where do mast cells mature?
CT and mucosa
What inactivates histamine?
histaminase
What does IL-1 do?
activates other inflammatory cells
What are the delayed effects of histamine?
white blood cell chemotaxis
Where do chemokines come from?
inflammatory cells, endothelial cells
What causes histamine release?
the antigen- IgE interaction of plasma cells
What cells make histamine?
mast cells, basophils, and platelets
Usually local, cell derived mediators are _____.
inflammatory
What is the mechanism of action for most chemical mediators?
receptor mediated
What are the immediate effects of histamine?
causes vasodilation, smooth muscle contraction, mucus secretion, and increased vascular permeability,
What synthesizes eicosanoids?
WBCs, platelets, endothelial cells
What is the time frame for acute inflammation?
minutes- hours
What are the major effects of eicosanoids?
1) vasodilation 2) vasoconstriction 3) vascular permeability 4) chemotaxis 5) platelet aggregation 6) smooth muscle contraction
What is the function of nNOS?
vasodilation, neurotransmitter release
What regulates the half life of NO?
the rate of synthesis
Liver, plasma derived mediators can be ____, ____, or _____.
coagulation factors/kinins, complement, acute phase proteins
What are the effects of the mediators on bronchial smooth muscle?
constriction
What is endocrine-like signaling?
a cell releases a signal that binds to receptors very far away; distant, systemic affects
Inflammatory cells lack ____ and ____, so they communicate via receptor-mediated signals.
cell junctions; synapses
What are the major effects of platelet activating factor?
1) platelet activation/stimulation 2) vasoconstriction 3) vasodilation and vascular permeability 4) chemotaxis and leukocyte activation 5) bronchospasm 6) neutrophil oxidative burst
Where does platelet activating factor come from?
platelets, neutrophils, basophils, mast cells, macs, endothelial cells
What are the systemic effects of TNF?
liver, anorexia, sleepiness, stimulates liver to make more acute phase proteins
What cells make cytokines?
lymphocytes, macs, EC
Where does interferon come from?
T lymphocytes, NK cells
What are the peptide mediators?
bradykinin, interleukins, tumor necrosis factor, substance P, cytoplasmic enzymes
What cells make platelet-activating factor?
all leukocytes, EC
What inactivates ROS?
superoxide dismutates, catalase, glutathione peroxidase, cerulolplasmin, transferrin
What are the eicosanoids derived from?
arachidonic acid/membrane phospholipids
What are the 3 kinds of NO and where to they come from?
1) iNOS (endothelium, smooth muscle, macs) 2) eNOS (endothelial cells) 3) nNOS (neural parenchyma)
Where do cytokines come from?
macs, lymphocytes, endothelial cells
Which cells store mediators?
neutrophils, macs
Where do local, cell derived mediators come from?
endothelial cells, nerve twigs, smooth muscle, epithelial cells, fibroblasts (the site of injury)
What is different about histamine and serotonin release?
histamine is immediately released; serotonin takes a release process
What inactivates stored mediators?
antiproteases
What are the important acute phase mediators?
TNF, IL-1, chemokines
What makes PAF acetyl hydrolases?
the liver and local inflammatory cells
Most mediators are _____.
local, cell derived
What does histamine do?
causes vasodilation, smooth muscle contraction, mucus secretion, increased vascular permeability, and white blood cell chemotaxis
Which chemical mediators use a direct affect?
RAS, lysosomal enzymes, macs and neutrophil granules
What does substance P do?
pain signaling, modulates vascular tone and permeability
What inactivates platelet activating factor?
PAF acetyl hydrolases
What cells make lysosomal enzymes?
neutrophils, macs
Where does interleukin come from?
macs
What are the effects of the mediators systemically/physiologically?
fever, pain, acute phase rxn
What are the oxygen-based mediators?
activated oxygen species, NO
What does serotonin do?
it’s similar to histamine
What is paracrine signaling?
cell releasing a signal that binds to a receptor on a nearby cell
What are some exogenous chemical mediators?
bacterial lipopolysaccharides, endotoxins, tissue debris
What are the amine mediators?
histamine, serotonin
What are the eicosanoids?
prostaglandins, leukotrienes, thromboxanes, lipoxins
What are the important chronic phase mediators?
interferon
What are the effects of the mediators on inflammatory cells?
chemotaxis, activation
What are the granules in stored mediators?
enzymes
What stimulates ROS release?
cytokines, endothelial cell damage
What are the local effects of TNF?
endothelial activation, thrombogenesis, fibroblast stimulation, activates other inflammatory cells, stimulates acute phase rxn
What causes serotonin release?
platelet aggregation due to collagen, thrombin, PAF, or TXA2
Where are prostaglandins made?
all leukocytes, platelets, EC
What cells make serotonin?
platelets
What are the functions of interferons?
activation of inflammatory cells, interfere w viral replication, tumor defense
What cells make NO?
macs
What is the effect of a single chemical mediator?
1) direct effects on specific tissues 2) cause release of other mediators 3) cause opposite effects
What kind of inflammation is typically associated with macs?
granulomatous
What causes TNF to be released?
bacterial endotoxins, immune complexes, tissue injury
Where does TNF come from?
activated macs, lymphocytes, mast cells
Which chemical mediators are made as-needed?
most of them
What cells make leukotrienes?
all leukocytes
Where do the reactive oxygen species come from?
leukocytes (macs, neutrophils), endothelial cells
What is the job of an eicosanoid?
signaling molecules
What is the time frame for repair?
days- weeks- months- years
What is NO formed from?
L-arginine by nitric oxide synthase
Which chemical mediators are pre-formed and stored in secretory vesicles?
histamine, serotonin, substance P, enzymes
What are the lipid mediators?
prostaglandins, leukotrienes, platelet activating factor
What is the time frame for chronic inflammation?
hours- days or longer
What are the 3 categories of chemical mediators of inflammation?
1) local, cell derived 2) liver, plasma derived 3) exogenous sources
What is the function of iNOS?
vasodilation, chemotaxis, toxic effects on microbes
What is the lifespan of a mediator?
usually short lived- rapidly degraded
Where does histaminase come from?
the liver, neutrophils, and macs
What is autocrine signaling?
cell releasing a signal that binds to a receptor on itself
What is the function of eNOS?
vasodilation, reduced leukocyte/platelet adhesion
What are the effects of the mediators on the blood vessels?
dilation, contraction, permeability
Name the 4 major types of inflammatory mediators (chemistry).
1) amine 2) lipids 3) peptides 4) oxygen based species
Where is substance P made?
nerve twigs in the lung or GI tract
