Veterinary General Pathology Dr. Laegreid Uiuc Exam 3

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Platelet Activating Factor

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source: lipid breakdown product from WBCs, platelets, vascular endothelium
function: platelet aggregation, adherance; increase vascular permeability; WBC enzyme release

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Macrophage Inflammatory Peptides (MIPs) (a type of chemokine)

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source: activated macrophages
function: stimulate macrophages, lymphocytes; activate fibroblasts

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Monocyte Chemoattractant Protein-1 (MCP-1) (a type of chemokine)

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source: endothelium, smooth muscle, activated macrophages
function: attract macrophages to site of inflammation

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Granulysin (a type of chemokine)

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source: cytotoxic T cells
function: kill pathogenic bacteria

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Transforming Growth Factor-beta (TGF-beta) (a type of chemokine)

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source: platelets, endothelium
function: stimulate collagen synthesis, enhance fibroblast activity

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Vascular Endothelial Growth Factor (VEGF) (a type of chemokine)

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source: most tissue cells except endothelium as this is the target
function: the major factor for angiogenesis in wound healing; increases vascular permability

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Platelet Derived Growth Factor (PDGF) (a type of chemokine)

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source: platelets, endothelium, macrophages
function: induction of fibroblast, monocyte,smooth muscle into the lesion

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Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF) (types of chemokines)

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important chemokines in healing processes

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Tumor Necrosis Factor alpha (TNF-alpha)

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source: activated macrophages, neutrophils, lymphocytes, NK cells, endothelial cells
function: acts w/ IL-1 to make fever; kill bacteria/protozoa directly; wasting effects; promotes scar tissue formation in persistent inflammation

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Tumor Necrosis Factor beta (TNF-beta)

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source: lymphocytes (cytotoxic T cells)
function: normal lymphoid development

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Interleukin 1 (IL-1alpha, IL-1beta)

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source: all nuecleated cells, especially endothelium, macrophages
function: synth of acute phase prots; adhesion expression by endothelium; neutrophil migration; affects hypothalamus-->fever; PG production; synergy w/ INF-gamma & IL-2; granuloma formation; bone/cartilage resorption

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IL-1 Receptor Antagonist (IL-1RA)

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source: activated macrophages
function: competitive inhibition of IL-1 receptor; dampens inflammatory response

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Interleukin 2, 15 (IL-2, IL-15)

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source: antigen stimulated TH1 cells
function: enhance cytotoxic T and NK cell activity

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Interleukin 3 (IL-3)

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source: activated T cells
function: potent hemopoietin; stimulates mast cells and macrophages to divide

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Interleukin 4, 13 (IL-4, IL-13)

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source: TH2 cells
function: work with IL-10 to suppress inflammation but enhance immune response; activation of additional T cells; stimulate Ab production by B cells; cause asthma

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Interleukin 5 (IL-5)

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function: eosinophil proliferation; only IL that is specific for eosinophils

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Interleukin 6 (IL-6)

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source: T cells, other inflammatory cells
function: stimulate hepatocytes to make acute phase proteins (w/ IL-1); stimulate IgA production; macrophage production by bone marrow

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Interleukin 8 (IL-8)

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source: macophages, fibroblasts, endothelium
function: most potent and important stimulator of neutrophil migration to sites of inflammation; stimulate neutrophil adhesion, activation, degranulation

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Interleukin 10 (IL-10)

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source: TH2 cells
function: major inhibitor of inflammation; with IL-2, 13, dampens inflammatory response; stimulates T and B cells, inhibits macrophages from making inflammatory CKs

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Interleukin 12 (IL-12)

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source: macrophages, B cells, neutrophils
function: stimulates cell-mediated immunity; stimulates TH1 and NK cells

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Interferon Alpha and beta (INF-alpha, INF-beta)

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source: WBCs, fibroblasts, lymphocytes
function: viral infection local response (non-specific, protective); slow spread of virus; inhibit protein synthesis of adjacent cells

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Interferon Gamma (INF-gamma)

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source: TH1, NK cells
function: most important activator of macrophages; causes inflammatory cells to express Fc and C3b receptors; enhances Ag processing and recognition

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Acute Phase Proteins

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fibrinogen, complement, iron-binding proteins, hepcidin, fibronectins
synthesized in the liver upon stimulation with IL-1, IL-6, TNF-alpha

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Fibrinogen (acute phase protein)

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source: hepatocytes
function: cleaved at site of inflammation to fibrin which walls off bacteria and provides scaffolding for repair; increases RBC aggregation

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Complement proteins (acute phase proteins)

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source: mostly liver, some from macrophages
function: opsonization of bacteria; neutrophil chemotaxis; increase vascular permability; lysis of cells

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Anaphylatoxins (C3a, C5a--from complement)

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release histamine from mast cells

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C3b (from complement)

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neutrophil chemoattractant (increases respiratory burst); opsonin (for neutrophils); stimulates lymphocytes to produce Ab and secrete macrophage chemotactic factors

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C5a (from complement)

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neutrophil chemoattractant (increases respiratory burst); release of lysosomal contents from neutrophils

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Lactoferrin (Iron-binding protein) (acute phase proteins)

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source: neutrophils
function: remove Fe from Fe-transferrin in tissue fluids; combine with toxic by-products to kill microbes via oxidization

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Hepcidin (acute phase proteins)

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source: hepatocytes
function: prevents iron uptake from gut by binding the uptake protein
causes anemia of chronic disease

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Fibronectins (acute phase proteins)

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important in Kupfer cell phagocytosis
plasma form function: opsonization, macrophage activation
tissue form function: linker between leukocytes or platelets and fibrin

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Eicosanoids

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derivatives of arachidonic acid: leukotrienes, prostaglandins

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Leukotrienes (eicosanoid)

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source: arachidonic acid breakdown of macrophages, neutrophils, eosinophils, basophils, mast cells
function: egress of WBCs out of vasculature

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LTA4 (leukotriene precursor) (eicosanoid)

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source: neutrophils
function: converted by other cell types to LTC4, LTD4, LTE4

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LTB4 (leukotriene) (eicosanoid)

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function: chemotactic for neutrophils; makes neutrophils sticky; promotes respiratory burst; stimulates B cell Ab production

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LTC4, LTD4, LTE4 (leukotrienes) (eicosanoids)

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function: increase vascular permability; act synergistically with LTB4; low concentraion--neutrophil chemotaxis; high concentration--oxygen metabolite formation; eosinophil chemotaxis; stimulate phospholipase

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Prostaglandins (eicosanoids)

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PGF2alpha, PGE2, PGD2
source: arachidonic acid breakdown; macrophages, platelets
function: vasodilation

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Kinins (bradykinin is the prototype)

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source: polypeptides derived from plasma protein precursors
function: potent, slow-acting vasodilation; increased capillary permeability; mediates pain; can cause release of histamine to start eicosanoid pathways

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Heparin

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source: mast cell and basophil granules
function: activates antithrombin III; inhibits platelet aggregation

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Vasoactive amines

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hsitamine, nitric oxide, serotonin

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Histamine (vasoactive amine)

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source: derivative of histidine stored in mast cell granules, platelets, basophils
function: 1st phase of vascular permeability--dilation of precapillary sphincters, endothelium rounding up/adhesion expression

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Serotonin (vasoactive amine)

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source:derivative of tryptophan stored in mast cells, platelets, basophils in lung, GIT, brain
function:mediate smooth muscle contraction and pain

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Nitric Oxide

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source: gas derived from arginine by activated macrophages, damaged endothelium, damaged tissue cells
function: physiologic--neurotransmitter, smooth muscle relaxation; pathologic--potent vasodilator; production of new blood vessels during healing