LYSMD3: A mammalian pattern recognition receptor for chitin.

Chitin, a major component of fungal cell walls, has been associated with allergic disorders such as asthma. However, it is unclear how mammals recognize chitin and the principal receptor(s) on epithelial cells that sense chitin remain to be determined. In this study, we show that LYSMD3 is expressed on the surface of human airway epithelial cells and demonstrate that LYSMD3 is able to bind chitin, as well as β-glucan, on the cell walls of fungi.

Development and application of novel immunoassays for eosinophil granule major basic proteins to evaluate eosinophilia and myeloproliferative disorders.

Background: During eosinophil differentiation, the granule eosinophil major basic protein 1 (eMBP1) is synthesized as a 32-kDa precursor form, referred to as proMBP1, which is processed into the 14-kDa mature form of eMBP1. The prevalence of these two forms of MBP1 in most pathological conditions remains unknown.

Objective: To develop the immunoassays that differentiate mature eMBP1 and proMBP1 and apply them to analyze their levels in biological fluids from patients with eosinophilia and hematologic disorders.

Fungal allergen-induced IL-33 secretion involves cholesterol-dependent, VDAC-1-mediated ATP release from the airway epithelium.

Key Points: Alternaria aeroallergens induce the release of ATP from human bronchial epithelial (HBE) cells by activating a conductive pathway involving voltage-dependent anion channel-1 (VDAC-1) and by exocytosis of ATP localized within membrane vesicles. Inhibition of VDAC-1 blocked Alternaria-evoked Ca uptake across the plasma membrane of HBE cells and interleukin (IL)-33 release into the extracellular media. Reducing cholesterol content with a cholesterol scavenger (β-methylcyclodextrin) or statin compound (simvastatin) blocked ATP and IL-33 release by lowering the expression of VDAC-1 in the plasma membrane.

An immunologic test for chronic rhinosinusitis based on free intranasal eosinophilic major basic protein.

Background: A histologic hallmark of chronic rhinosinusitis (CRS) is an eosinophilic inflammation, present with and without nasal polyposis and independent of atopy. Eosinophils migrate through nasal tissue including the epithelium into the nasal airway mucus, where they form clusters and degranulate, releasing granule proteins including the toxic major basic protein (MBP). Specific biomarkers for CRS, which could be used as a diagnostic test for CRS with a high sensitivity and specificity, are presently lacking.

IL-33-activated dendritic cells induce an atypical TH2-type response.

Background: IL-33, a recently discovered IL-1 family cytokine, is implicated in the development of T(H)2-type responses in vivo. However, the cellular targets for IL-33 are poorly understood.

Objective: We tested the hypotheses that dendritic cells (DCs) respond to IL-33 and that IL-33-activated DCs prime naive CD4(+) T cells to produce T(H)2-type cytokines.

Pimecrolimus reduces eosinophil activation associated with calcium mobilization.

Background: Pimecrolimus is a calcineurin inhibitor that inhibits T cell and mast cell activation and effectively treats atopic dermatitis. However, its effects on eosinophils, a cell type implicated in allergic disease pathology, are unknown. Therefore, we examined the effects of pimecrolimus on eosinophil superoxide anion production, degranulation and survival.

Clinical correlates of serum pro-major basic protein in a spectrum of eosinophilic disorders and myelofibrosis.

Background/aims: Eosinophil cytoplasmic granules contain major basic protein (MBP), which is primarily translated from its precursor, proMBP. In this study, we evaluated the plasma level of proMBP in eosinophilic and chronic myeloproliferative disorders (MPN).

Methods: The levels of plasma proMBP were measured by radioimmunoassay in 25 healthy controls, 23 patients with systemic mastocytosis (SM), 11 patients with idiopathic eosinophilia (IE) and a cohort of 170 patients with MPN which included 76 patients with de novo myelofibrosis, 42 with polycythemia vera (PV), 17 with postpolycythemic myeloid metaplasia (Post-PV MF), 21 with essential thrombocythemia (ET) and 14 with postthrombocythemic myeloid metaplasia (Post-ET MF).