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Granulocytes

Granulocytes. They participate in inflammatory reaction, and can be called inflammatory cells 。 By differential staining characterization of the granules ， they are different from neutrophils and each granule cell 。. Inflammatory cells ：

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Granulocytes

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  1. Granulocytes • They participate in inflammatory reaction, and can be called inflammatory cells。 • By differential staining characterization of the granules，they are different from neutrophils and each granule cell。 • Inflammatory cells： • They are applicable to many different cell types；some are long-term residents of normal tissues (such as mast cells and macrophages)，others are circulating cells (such as lymphocytes, neutrophils, eosinophils, basophils, and platelets)。

  2. Granulocytes • Most of inflammatory cells express surface receptors for complement components, for the Fc portions of antibody molecules, and for various cytokines。 • Their activities tend to be controlled directly or indirectly by ongoing immune responses or by activation of the complement cascade。

  3. Mast cells • The granules of mast cells contain an acid porteoglycan；在人體其大小為5-7 um in diameter，且具有不同種外形；每一個細胞內約有50-200個packed granules。 • Each granule is membrane-bounded and 0.1- 0.4 um in diameter, and contains relatively large amounts of histamine, heparin, TNF-α, and other preformed inflammatory mediators；also contains superoxide dismutase, peroxidase, and acid hydrolases to degrade the extracellular matrix。 • 主要出現於perivascular connective tissue、epithelia及lymph nodes，容易與呼吸道及食道抗原接觸，因其granules染色特徵 (包含之中性proteases種類不同) 可分為：

  4. Mucosal mast cells(MMC)：具有一些與basophils相似得特徵，如細胞較小、生命期短、以chondroitin sulphate作為acid porteoglycan、需T細胞協助其細胞生長及分化等。 • Connective tissue mast cells(TCMC)。 • 具有anaphylatoxins (C3a、C5a)分子的受器。 • 為IgE-mediated inflammatory reaction所必須的細胞，因此其細胞表面具有許多和IgE Fc親和性高之表面受器(FcεRI)。 • 當其表面IgE與抗原接觸，促使mast cell活化進行degranulation，將granule中的物質釋放出來，這些物質中有些可以促使細胞通透性增加、平滑肌收縮及促發炎細胞發生化學遷移，這些物質被稱為mast cell mediators。

  5. Mast cell mediators • Preformed mediators： • Histamine：刺激平滑肌收縮及增加血管通透性。 • eosinophil and neutrophil chemotactic factors(ECF and NCF)：與其他granulocytes作用，增加granulocyte細胞C3表面受器的形成；刺激影響呼吸作用產生含氧化合物形成。 • proteoglycan：如heparin是一種anticoagulant及anticomplementary，可以克服凝結作用，促進mast cell mediator diffusion。 • acid hydrolase • neutral proteases

  6. Mast cell mediators • Secondary mediators：Slow reacting substance (SRS) • Lipid derivatives of arachidonic acid，有Slow reacting substance (SRS，three different leukotrienes (LTC4、LTD4、LTE4))、LTB4 (chemotactic agent)、prostaglandins (PGE2、PGD2、PGF2α)、platelet activating factor (PAF)。 • arachidonic acid metabolism pathway： • cyclo-oxygenase(prostaglandin synthetase) path • lopoxygenase path • cytokines • tumor necrosis factor-α(TNF-α)：proinflammatory cytokine。 • chemokines：IL-8 (proinflammatory cytokine)，IL-4(to promote B細胞經switching產生IgE)、IL-5 (to promote the differentiation and activation of eosinophils)。

  7. Basophils • The granules of basophils contain an acid porteoglycan。 • 為循環細胞之一，與mast cell具有多項相同的作用。 • 大小為10-15 um in diameter。 • 細胞表面具有許多和IgE Fc親和性高之表面受器(FcεRI)，及含有histamine-rich cytoplasmic granules。 • 正常情況下，basophil在組織的含量很低；the importance of basophils in immunity and hypersensitivity has yet to be proven。

  8. Eosinophils • The granules of eosinophils contain several basic proteins。 • Their clinical significance derives from their strong association with allergic reaction and with helminthic parasite infection。 • 人類的eosinophils大小約為12-17 um in diameter，具有少量的specific granules，每個granule大小約為0.5 um in diameter。 • granule中主要含有eosinophil peroxidase(EPO)、other enzymes that can generate toxic oxygen metabolites、basic proteins(其中有一種稱為major basic protein與acidic dyes，如eosin，具有高親和性，染成紅色的granule)；不具有lysozyme。

  9. Eosinophils • granule中之氧化作用主要產生H2O2及superoxide，不確定是否會產生oxygen radicals。 • EPO is able to work in concert with hydrogen peroxide and iodide or chloride ions to lys some microorganisms。 • Basci proteins (cationic proteins) are the major source of lytic activity in the eosinophils。 • 其他酵素，如histaminase，β-glucuronidase，phospholipase D，其作用尚未明白。 • 許多由eosinophils產生的物質對mast cell mediators有抑制作用，可能具有抗發炎作用。

  10. Eosinophils • 佔循環系統中白血球量的1-3%，其發生受到granulocyte-macrophage colony-stimulating factor(CM-CSF)、IL-3及IL-5的影響，其中IL-5為specific eosinophil growth factor。 • 在骨髓成熟期約為2-6天，進入循環系統期半生期約為6-12小時，在結締組織僅可生活數小時。 • 表面具有IgE Fc受器(FcεRII)，期親和性低；約有10-30%的eosinophils具有親和性低的FcγRIII及中親和性的FcγRII；40-50%的eosinophils具補體受器；藉此使eosinophils認識許多種抗原及被IgE及IgG包裹的細胞，而促使吞噬細胞進行吞噬。 • 研究顯示eosinophil稍具有吞噬作用，其可藉由extracellular degranulation將被抗體包裹的細胞或外來顆粒消化。

  11. Mediators of inflammation • Host-derived compounds that are secreted by activated cells and serve to trigger or enhance specific aspects of inflammation。 • Many of the cytokines act as inflammatory mediators，other major inflammatory mediators are classified into four groups： • Vasoactive and smooth muscle-constricting mediators • Chemotactic factors • Enzymatic mediators • Proteoglycan mediators

  12. Mediators of inflammation • Types of immunologically inflammatory responses • Cell-mediated immunity(CMI) • Immune complex-mediated inflammation • IgE-mediated inflammation • Cutaneous basophil hypersensitivity

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