Mechanisms of eosinophilic inflammation

Abstract

Eosinophils play roles in the pathogenesis of various diseases. In order to accumulate within sites of inflammation, eosinophils must adhere to, and migrate across the microvasculature. These processes are largely controlled by type 2-immune responses; interleukin (IL)-4 and IL-13 induce the expression of endothelial adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), a representative adhesive ligand for eosinophils, while also stimulating generations of CC chemokines from structural cells, including epithelial cells. VCAM-1 and CC chemokines synergistically induce transmigration of eosinophils to the tissue inflammation site. Another type 2 cytokine, IL-5, prolongs survival, and enhances the effector functions of eosinophils. Recently, accumulating evidence has established that corticosteroid-resistant group 2 innate lymphoid cells are cellular sources for IL-5. Another immunological mechanism that may be contributing to eosinophilic inflammation involves type 1 immune system-associated molecules such as interferons and IP-10. In addition to these immune pathways, lipid mediators, such as cysteinyl leukotrienes, directly provoke the infiltration and activation of eosinophils. Extracellular matrix proteins including periostin also induce the adhesion and activation of eosinophils. Finally, activated neutrophils can also induce eosinophil transmigration. In summary, various mechanisms are involved within eosinophilic inflammation, and effective therapeutic strategies targeting these pathways should be established.

Kawasaki Disease and Allergic Diseases

“…IL-31 has also been reported to be involved in Th2-mediated diseases, such as allergic diseases, as well as KD ( 32 ). Eosinophils play an important role in type 2 inflammation ( 33 ). Previous studies have reported that patients with KD had higher eosinophils, Th2 cytokines IL-4, IL-5, and eosinophil cationic protein (ECP) levels than controls ( 17 , 25 ).…”

Eosinophils and Purinergic Signaling in Health and Disease

“…While in healthy subjects the number of eosinophils in the peripheral blood is low, it can increase dramatically under pathophysiological conditions such as atopic dermatitis, bronchial asthma, eosinophilic esophagitis, gastritis, gastroenteritis, colitis or hematological malignancies ( 54 , 62 , 71 , 80 , 123 ). The large body of evidence supporting the critical role of eosinophils in parasitic and inflammatory diseases has prompted and intensified investigations on potential targets to modulate cellular responses of eosinophils.…”

“…Eosinophils themselves produce different cytokines including IL-1, IL-3, IL-4, IL-5, IL-6, IL-8, TNF-α, TGF-β, GM-CSF and pro-inflammatory mediators such as leukotriene C4 (LTC4), platelet-activation factor (PAF) ( 71 , 74 ), the granular cationic proteins, major basic protein (MBP) 1, MBP 2, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPO). MBP which is present in the crystal core of the specific granules has cytotoxic effects due to interference with electrical properties and permeability of the cell membrane.…”

Immunological Roles of NLR in Allergic Diseases and Its Underlying Mechanisms

“…NOD2 ligand MDP can activate BEAS-2B cells and human basophils by stimulating their release of inflammatory cytokines, including Th17-polarizing IL-6, and upregulating the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in the co-culture of basophils and bronchial epithelial cells through NF-κB, c-Jun N-terminal kinases (JNK) and p38 MAPK pathways [12]; hence, magnifying the inflammatory response. ICAM-1 and VCAM-1 are essential for leucocytes migration to the inflammatory sites in allergy, with expressions that are positively correlated with allergic asthma severity [12,108]. MDP can also induce the release of antimicrobial peptide β-defensin 2 from the bronchial epithelial cells in the co-culture of human basophils and human bronchial epithelial cells [12].…”