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Slide 1 - Chemical Mediators of Inflammation Francisco G. La Rosa, MD Francisco.LaRosa@ucdenver.edu Associate Professor, Department of Pathology University of Colorado Denver, Aurora, Colorado 80045 University of Colorado Denver School of Medicine Disease & Defense (Course IDTP5004A)
Slide 2 - ppt slide no 2 content not found
Slide 3 - Leukocyte activation. Different classes of cell surface receptors of leukocytes recognize different stimuli. The receptors initiate responses that mediate the functions of the leukocytes. Only some receptors are depicted.
Slide 4 - Click for Movie NECROSIS: A white blood cell dies after a meal Ingesting “leukotoxic” Streptococcus pyogenes
Slide 5 - Reactions are similar irrespective of tissue or type of injury 2. Reactions occur in absence of nervous connections “Chemical substances mediate all phases of acute inflammation” Thomas, Lewis (1913-1993)
Slide 6 - Chemical mediators of inflammation (EC: endothelial cells)
Slide 7 - Vasodilatation: Histamine Prostaglandins Nitric oxide Increased vascular permeability: Histamine Anaphylatoxins C3a and C5a Kinins Leukotrienes C, D, and E PAF Substance P Chemotaxis: Complement fragment C5a Lipoxygenase products, lipoxins & leukotrines (LTB4) Chemokines Tissue Damage Lysosomal products Oxygen-derived radicals Nitric Oxyde Events in Acute Inflammation
Slide 8 - Prostaglandins : Vasodilation Pain Fever Potentiating edema IL-1 and TNF: Endothelial-leukocyte interactions Leukocyte recruitment Production of acute-phase reactants Diversity of Effects of Chemical Mediators
Slide 9 - VASODILATATION
Slide 10 - Basophils & Mast Cells
Slide 11 - Adipose tissue showing mast cells around blood vessels and in the interstitial space. Stained with metachromatic stain to identify the mast cell granules (dark blue or purple). The red structures are fat globules stained with fat stain (oil red)
Slide 12 - Mast Cells & Allergy
Slide 13 - Ultrastructure and contents of neutrophil granules, stained for peroxidase activity. The large peroxidase-containing granules are the azurophil granules; the smaller peroxidase-negative ones are the specific granules (SG). N, portion of nucleus.
Slide 14 - LEUKOTRINES & PROSTAGLANDINS
Slide 15 - Leukotrienes and Prostaglandins: Potent mediators of inflammation Derived from Arachidonic acid (AA): 20-carbon, unsaturated fatty acid produced from membrane phospholipids. Principal pathways: 5-lipoxygenase: Produces a collection of leukotrienes (LT) Cyclooxygenase (COX): Produces prostaglandin H2 (PGH2) PGH2 serves as substrate for two enzymatic pathways: Prostaglandins (PG) Thromboxanes (Tx).
Slide 16 - Biosynthesis of leukotrienes and lipoxins by cell-cell interaction. AA: arachidonic acid –derived; LTA4: Leukotriene A4; LTC4: Leukotriene C4
Slide 17 - NITRIC OXIDE
Slide 18 - Functions of nitric oxide (NO) in blood vessels and macrophages, produced by two NO synthase enzymes. NO causes vasodilation, and NO free radicals are toxic to microbial and mammalian cells. NOS: nitric oxide synthase.
Slide 19 - IL-1 & Tumor Necrosis Factor (TNF)
Slide 20 - Major effects of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in inflammation
Slide 21 - COMPLEMENT
Slide 22 - Complement Activation Pathways
Slide 23 - The activation and functions of the complement system. Activation of complement by different pathways leads to cleavage of C3. The functions of the complement system are mediated by breakdown products of C3 and other complement proteins, and by the membrane attack complex (MAC)
Slide 24 - OXYGEN FREE RADICALS
Slide 25 - Production of microbicidal reactive oxygen intermediates within phagocytic vesicles.
Slide 26 - OXIDATIVE BURST: Neutrophils kill microbes by producing reactive oxygen species, demonstrated here with the dye nitroblue tetrazolium (NBT) Click for Movie
Slide 27 - Interrelationships between the four plasma mediator systems triggered by activation of factor XII (Hageman factor). Note that thrombin induces inflammation by binding to protease-activated receptors (principally PAR-1) on platelets, endothelium, smooth muscle cells, and other cells.
Slide 28 - Role of Mediators in Different Reactions of Inflammation
Slide 29 - ppt slide no 29 content not found
Slide 30 - Generation of arachidonic acid metabolites and their roles in inflammation. The molecular targets of some anti-inflammatory drugs are indicated by a red X. COX, cyclooxygenase; HETE, hydroxyeicosatetraenoic acid; HPETE, hydroperoxyeicosatetraenoic acid.
Slide 31 - Prostaglandin Arachidonic acid Eicosanoid Eicosanoids Leukotriene Prostacyclin Thromboxane Thromboxane-A synthase Essential fatty acid interactions Leukotriene B4 Leukotriene E4 Prostacyclin synthase Leukotriene A4 Leukotriene D4 Leukotriene C4 Thromboxane A2 Arachidonate 5-lipoxygenase Prostaglandin H2 Prostaglandin E synthase Arachidonic acid 5-hydroperoxide Leukotriene C4 synthase GLOSSARY abscess acute inflammation adhesion molecules chemokinesis chemotactic agent chemotaxis chronic inflammation contact inhibition degranulation empyema emigration eosinophil erosion exudate fibrin/fibrinous fibrinogen fibrous/fibrosis free radicals granulation tissue granuloma hyperemia infection keloid left shift leukocyte leukemoid reaction leukocytosis lymphocyte lysosomes macrophage (AKA...) margination myeloperoxidase neutrophil neutrophilia opsonization organization phagocytosis plasma cell pseudomembrane purulent pus regeneration resolution scar suppurate transudate ulcer
Slide 32 - Disclaimer: The images and texts presented in this slide show are solely for educational purposes and not intended for commercial or pecuniary benefit. The images have been obtained from Dr. La Rosa’s personal collection, from text books used during the teaching of this chapter, and from published articles and educational works. Reproduction of these images can be done only for educational use. Reference: USA Copyright Law, Section 110, “Limitations on exclusive rights: Exemption of certain performances and displays”). [Download] the USA Copyright Law version, October 2009.