title: Eosinophil granule proteins: form and function.
abstract: Experimental and clinical data strongly support a role for the eosinophil in the pathogenesis of asthma, allergic and parasitic diseases, and hypereosinophilic syndromes, in addition to more recently identified immunomodulatory roles in shaping innate host defense, adaptive immunity, tissue repair/remodeling, and maintenance of normal tissue homeostasis. A seminal finding was the dependence of allergic airway inflammation on eosinophil-induced recruitment of Th2-polarized effector T-cells to the lung, providing a missing link between these innate immune effectors (eosinophils) and adaptive T-cell responses. Eosinophils come equipped with preformed enzymatic and nonenzymatic cationic proteins, stored in and selectively secreted from their large secondary (specific) granules. These proteins contribute to the functions of the eosinophil in airway inflammation, tissue damage, and remodeling in the asthmatic diathesis. Studies using eosinophil-deficient mouse models, including eosinophil-derived granule protein double knock-out mice (major basic protein-1/eosinophil peroxidase dual gene deletion) show that eosinophils are required for all major hallmarks of asthma pathophysiology: airway epithelial damage and hyperreactivity, and airway remodeling including smooth muscle hyperplasia and subepithelial fibrosis. Here we review key molecular aspects of these eosinophil-derived granule proteins in terms of structure-function relationships to advance understanding of their roles in eosinophil cell biology, molecular biology, and immunobiology in health and disease.
authors.affiliation: From the Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom and K.R.Acharya@bath.ac.uk.
authors.forename: K Ravi
authors.initials: KR
authors.lastname: Acharya
authors.affiliation: the Department of Biochemistry and Molecular Genetics, College of Medicine, The University of Illinois, Chicago, Illinois 60607 sackerma@uic.edu.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ackerman
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003920:Diabetes Mellitus / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D047093:Eosinophil Major Basic Protein / Q000235:genetics / Q000276:immunology*; D047209:Eosinophil Peroxidase / Q000235:genetics / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D013329:Structure-Activity Relationship; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D047209:Eosinophil Peroxidase; D047093:Eosinophil Major Basic Protein
keywords: Asthma; Crystal Structure; Enzyme Structure; Eosinophil; Eosinophil Granule Proteins; Inflammation