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2014 ; 289
(25
): 17406-15
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Eosinophil granule proteins: form and function
#MMPMID24802755
Acharya KR
; Ackerman SJ
J Biol Chem
2014[Jun]; 289
(25
): 17406-15
PMID24802755
show ga
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.
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