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Vol. 51, Issue 2, 213-340, June 1999

Pharmacology of the Eosinophil

Mark A. Giembycz1 and Mark A. Lindsay

Thoracic Medicine, Imperial College School of Medicine at the National Heart & Lung Institute, London, United Kingdom

I. Introduction and Historical Perspective
II. Gross Morphology and Ultrastructure
III. Life Cycle, Maturation, and Tissue Distribution
IV. Transcription Factors and Eosinophilia
V. G Protein-Coupled Receptors and Their Ligands
    A. Platelet-Activating Factor
        1. Receptors and Signaling.
        2. In Vitro Effects.
        3. In Vivo Effects.
    B. Leukotriene B4
        1. Receptors and Signaling.
        2. In Vivo Effects.
    C. Cysteinyl Leukotrienes
        1. In Vitro Effects.
        2. In Vivo Effects.
    D. N-Formyl-Methionyl-Leucyl-Phenylalanine
    E. Chemokines
        1. CC Chemokines.
        2. CXC Chemokines.
    F. Complement
        1. Complement 3a Anaphylatoxin.
        2. Complement 4a Anaphylatoxin.
        3. Complement 5a Anaphylatoxin.
    G. 5-Oxoeicosatetraenoic Acid (ETE), Hydroxyeicosatetraenoic Acids (HETEs), and Dihydroxyeicosatetraenoic Acids (diHETEs)
    H. Sensory Neuropeptides
        1. Substance P.
        2. CGRP.
        3. Secretoneurin.
        4. Vasoactive Intestinal Peptide.
    I. Bradykinin
    J. Endothelin
    K. Adenosine
    L. Histamine
    M. Prostanoids
    N. alpha  Adrenoceptors
    O. beta  Adrenoceptors
        1. Receptors.
        2. Activation of the NADPH Oxidase.
        3. Degranulation.
        4. Chemotaxis and Chemokinesis.
        5. Adhesion and Adhesion Molecule Expression.
        6. Membrane Lipid Metabolism.
        7. Homotypic Aggregation.
        8. In Vivo Effects.
    P. Somatostatin
    Q. Lipoxins
VI. Interleukin-3, Interleukin-5, and Granulocyte/Macrophage Colony-Stimulating Factor
    A. Receptor Expression and Regulation
    B. Signal Transduction
    C. Functional Effects
VII. Interferon Receptor Superfamily
VIII. Tumor Necrosis Factor Superfamily
    A. Tumor Necrosis Factor alpha
    B. CD30 Ligand
    C. CD40 and CD40 Ligand
    D. CD69
    E. CD95
    F. Nerve Growth Factor
IX. Adhesion Molecules
    A. Selectins
    B. Integrins
        1. beta 1 Integrins.
        2. beta 2 Integrins.
        3. alpha 4beta 7 Integrin.
    C. Intercellular Adhesion Molecule 1
X. Immunoglobulins
    A. Receptors for Fcalpha
    B. Receptors for Fcdelta and Fcµ
    C. Receptors for Fcepsilon
    D. Receptors for Fcgamma
XI. Miscellaneous
    A. Interleukin-1
    B. Interleukin-2
    C. Interleukin-4
    D. Interleukin-10
    E. Interleukin-12
    F. Interleukin-13
    G. Transforming Growth Factor beta
    H. Platelet-Derived Growth Factor
    I. Stem Cell Factor
    J. CD4
    K. CD9
    L. CD44
    M. CD52
    N. Complement Receptors Not Coupled Through G Proteins
        1. CR1.
        2. CR3.
        3. CR4.
        4. The C1q Receptor.
    O. Melittin
    P. Secretory Component
    Q. Human Leukocyte Antigen
XII. Functional Consequences of Eosinophil Activation
    A. Locomotion
        1. Rolling.
        2. Adhesion.
        3. Transmigration and Chemotaxis.
    B. Cytolysis, Secretion, and Piecemeal Degranulation
    1. Granule Proteins
    2. Morphological Changes
        3. Cell-Signaling Events.
        4. Electrophysiological Changes.
    C. Generation of Lipid Mediators
        1. Platelet-Activating Factor.
        2. Cyclooxygenase Products.
        3. 5-Lipoxygenase Products.
        4. 12-Lipoxygenase Products.
        5. 15-Lipoxygenase Products.
        6. Lipoxins.
        7. Lipid Bodies as Sites of Eicosanoid Formation.
    D. Generation of Cytokines
        1. Interleukin-1alpha .
        2. Interleukin-2.
        3. Interleukin-3.
        4. Interleukin-4.
        5. Interleukin-5.
        6. Interleukin-6.
        7. Interleukin-10.
        8. Interleukin-12.
        9. Interleukin-16.
        10. Interferon-gamma .
        11. Tumor Necrosis Factor alpha .
        12. Granulocyte/Macrophage Colony-Stimulating Factor.
        13. Macrophage Migration Inhibitory Factor.
    E. Generation of Chemokines
        1. Interleukin-8.
        2. Macrophage Inflammatory Protein 1alpha .
        3. RANTES.
        4. Eotaxin.
    F. Generation of Growth Factors
        1. Transforming Growth Factor alpha .
        2. Transforming Growth Factor beta 1.
        3. Platelet-Derived Growth Factor.
        4. Heparin-Binding, Epidermal Growth Factor-Like Growth Factor.
        5. Vascular Endothelial Growth Factor.
        6. Nerve Growth Factor.
    G. Activation of the NADPH Oxidase
    H. Apoptosis
XIII. Eosinophil Heterogeneity
    A. Physical Heterogeneity
    B. Functional Heterogeneity
        1. Cell-Cell Interactions.
        2. Up-Regulation of Cell Surface Receptors.
    C. Morphological Heterogeneity
    D. Acquisition of a Hypodense Phenotype
XIV. Pharmacological Modulation of Eosinophil Function
    A. Phosphodiesterase Inhibitors
        1. Enzymology.
        2. Activation of the NADPH Oxidase.
        3. Degranulation.
        4. Adhesion and Adhesion Molecule Expression.
        5. Chemotaxis and Chemokinesis.
        6. Synthesis of Lipid Mediators.
        7. Apoptosis.
        8. In Vivo Effects.
    B. Theophylline
        1. In Vitro Effects.
        2. In Vivo Effects.
    C. Cholera Toxin and Forskolin
    D. Cyclic Nucleotide Analogs
    E. Glucocorticosteroids
        1. Receptors.
        2. Maturation.
        3. Adhesion and Adhesion Molecule Expression.
        4. Cell Survival and Apoptosis.
        5. Degranulation.
        6. Chemotaxis.
        7. Effects on Transcription of Genes Relevant to Eosinophil Function.
        8. Activation of the NADPH Oxidase.
        9. Antigen Presentation.
    F. Estrogen
    G. Lazaroids
    H. Retinoids
    I. Cromones
    J. Loop Diuretics
    K. Sodium Channel-Blocking Drugs
    L. Ketotifen
    M. Cyclosporin A, Tacrolimus, and Rapamycin
        1. In Vitro Effects.
        2. In Vivo Effects.
    N. Nitric Oxide
        1. Apoptosis.
        2. Chemotaxis.
        3. In Vivo Effects.
    O. Cetirizine and Other Second-Generation Histamine H1 Receptor Antagonists
XV. Concluding Remarks
Acknowledgments
References

1   Address for correspondence: Thoracic Medicine, Imperial College School of Medicine at the National Heart & Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom. E-mail: m.giembycz{at}ic.ac.uk

0031-6997/99/5102-0213$03.00/0
PHARMACOLOGICAL REVIEWS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


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J. Biol. Chem., April 6, 2000; 275(15): 10968 - 10975.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
D. C. Underwood, R. R. Osborn, C. J. Kotzer, J. L. Adams, J. C. Lee, E. F. Webb, D. C. Carpenter, S. Bochnowicz, H. C. Thomas, D. W. P. Hay, et al.
SB 239063, a Potent p38 MAP Kinase Inhibitor, Reduces Inflammatory Cytokine Production, Airways Eosinophil Infiltration, and Persistence
J. Pharmacol. Exp. Ther., April 1, 2000; 293(1): 281 - 288.
[Abstract] [Full Text]


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