Eosinophil Granule Proteins: Form and Function [Immunology]

May 6th, 2014 by Acharya, K. R., Ackerman, S. J.

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 non-enzymatic cationic proteins, stored in and selectively secreted from their large secondary (specific) granules. These proteins contribute to the eosinophil's functions in airway inflammation, tissue damage and remodeling in the asthmatic diathesis. Studies using eosinophil deficient mouse models, including eosinophil-derived granule protein double knockout 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 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, molecular and immunobiology in health and disease.