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mast cells in lung tissue

mast cells in lung tissue. basophil. Basophil and Mast cell : introduction. bone marrow derived granulocytes myeloid lineage Paul Ehrlich 1879 deep violet blue metachromatic acidic mambrane-bound granules basophils usually less than 0.2% of WBC secretory function. mast cell : function.

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mast cells in lung tissue

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  1. mast cells in lung tissue

  2. basophil

  3. Basophil and Mast cell : introduction • bone marrow derived granulocytes • myeloid lineage • Paul Ehrlich 1879 deep violet blue metachromatic acidic mambrane-bound granules • basophils usually less than 0.2% of WBC • secretory function

  4. mast cell : function • distributed in organs which interface with exterior: lung, nasal tissue, skin, gut. • sentinel or surveillance function • increase (mast cell hyperplasia) associated with • parasite infections • allergy • mastocytoma (rare) • increase in blood precursors - basophils

  5. Mast cell : IL-3, 4 and SCF (c-KitL) • Mast cell recruitment, proliferation, maturation and maintenance requires the stromal cell and autocrine growth factor stem cell factor (c-kit ligand) and IL-6 • Chemotaxis to SCF, TGF, MCP-1, chemokine-fractaline. • T-cell derived IL-3 and IL-4/13 seem to be required for differentiation • Secretagogues (IL-3, neuropeptides NGF and substance P) may act by releasing endogenous SCF • SCF stimulation inhibited by TGF • IL-3/4 differentiation inhibited by GM-CSF

  6. Mast cell : connective tissue (CTMC) and mucosal (MMC) CTMC MMC • location ubiquitous lung, gut • granules/cell 20 uniform 10 variable sized • histamine/cell 15 pg 1.3 pg • LTC4/PGD2 1:40 25:1 • lifespan >6 months <40 days • anti-allergic drugs susceptible relatively resistant • T cell -independent -dependent • fixation saffranin alcian blue • proteoglycan heparin chondroitin sulphate • protease tryptase plus chymotryptase • IgE staining surface cytoplasm + surface • compound 48/80 susceptible resistant

  7. IMMUNOLOGICAL: Allergen-IgE FcER1 cross linking Antigen-IgG2a / IgG4 FcgammaR cross linking. Anaphylotoxins: C3a C5a Eosinophil major basic protein. NON-IMMUNOLOGICAL: Substance-P, NGF Polymyxin-B Compound 48/80 (CTMC) Venoms Irradiation and heat Cytokines: SCF (c-Kit ligand); GM-CSF; (IL-3/IL-4/IL-13). Mast cell : receptors and degranulation

  8. Mast cell degranulation

  9. Pre-formed Histamine Eosinophil chemotactic factor of anaphylaxis (ECF-A) Val-Gly-Ser-Glu and Ala-Gly-Ser-Glu Neutrophils - LTB4 Neutral proteinases, tryptase, chymotryptase Oxidative enzymes Granule matrix proteoglycans: heparin or chondroitin sulphate Newly-generated Lipid mediators Arachadonic acid metabolites: PGD2 LTB4, C4, D4, E4. Platelet activating factor (PAF). CytokinesTNF-a, TGF-b, IL-6, IL-3, IL-4, IL-5, IL-9, IL-10, IL-13, IL-8, (IFN-g). Mast cell : mediators

  10. Mast cell : mediator function Vaso-dilatation, smooth muscle contraction • histamine - immediate, prostanoids - prolonged Inflammation • eosinophil and neutrophil chemotactic factors • oxidative enzymes • cytokines Tissue remodelling • granule matrix proteoglycans • neutral proteinases, collagenase

  11. Mast cell : protective function against parasites • mast cell hyperplasia and IgE super-abundance is common in nematode infection • mast-cell deficient or IgE knock-out mice seem equally able to eliminate parasitic nematodes • anti-gram negative bacterial function noted in mouse coecal pouch model

  12. mast cells protect against bacterial infection • Mast cell produce TNFalpha on contact with bacterial fimbriae (Klebsiella pneumoniae) • TNF stimulates recruitment of neutrophils and macrophages which engulf bacteria. • NO controls MC mediator release • Echtenacher, B. Nature 1996;381:75-80 • Prodeus et al. Nature 1997;390: 172-5

  13. Mast cell : pathogenic role in allergy • site-specific mast cell hyperplasia and specific IgE abundance is common in allergic disease • anti-mast cell therapies are effective in allergy - anti-histamines, steroids, cromoglycate

  14. mast cells and nerves

  15. Mast cell : summary • distributed mainly for surveillance. • regulate acute inflammatory reactions by rapid production of mediators:via IgE - immediate hypersensitivity.via antibody-independent mechanisms e.g. pathogen products • amplify innate immune/inflammatory responses by recruiting effector cells from the blood • histamine and prostanoids increase vascular permeability • proteases modulate local tissue environment/remodelling • proteases increase permeability of epithelial cells. • heterogeneity indicates tissue-specific adaptation for local function • mast cells have a role in protective responses possibly when localised to micro-environments and when mediator concentrations are low - deleterious anaphylaxis may be due to rapid and generalised production of large quantities of mediators within a tissue.

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