RationaleAcute lung injury (ALI) is a fatal but undertreated condition with severe neutrophilic inflammation, while little is known about the functions of eosinophils in pathogenesis of ALI.ObjectivesTo investigate the roles and molecular mechanisms of eosinophils in ALI.MethodsPulmonary eosinophils were identified by flow cytometry. Mice with abundant or deficient eosinophils were used. Cellularity of eosinophils and neutrophils in BALF, inflammatory assessment, and survival rate were detected. Human samples were also used for validating experimental results.ResultsBlood eosinophils were increased in survived individuals of patients with acute respiratory distress syndrome independent of the corticosteroid usage. There existed homeostatic eosinophils in lung parenchyma in mice, and these homeostatic eosinophils in originating from the bone marrow were predominantly CD101−. More CD101− eosinophils could be recruited earlier than lipopolysaccharide (LPS)-initiated neutrophilic inflammation. Loss of eosinophils augmented LPS-induced pulmonary injury. Homeostatic CD101− eosinophils ameliorated, while allergic CD101+ eosinophils exacerbated, the neutrophilic inflammation induced by LPS. Likewise, CD101 expression in eosinophils from ARDS patients did not differ from the healthy subjects. Mechanistically, CD101− eosinophils exhibited higher levels of Alox15 and Protectin D1. Administration of Protectin D1 isomer attenuated the neutrophilic inflammation.ConclusionsCollectively, our findings identify an uncovered function of native CD101− eosinophils in suppressing neutrophilic lung inflammation and suggest a potential therapeutic target for ALI.

IntroductionEosinophils are critical in allergic disorders, and promoting eosinophil death effectively attenuates allergic airway inflammation. Ferroptosis is a recently described novel form of cell death; however, little is known about ferroptosis in eosinophils and related diseases. This study aimed to investigate the effects of ferroptosis-inducing agents (FINs) on eosinophil death and allergic airway inflammation, and to explore their potential synergistic effect with glucocorticoids (GCs).MethodsEosinophils isolated from the peripheral blood of humans or mice were incubated with FINs, and eosinophil ferroptosis was assessed. The in vivo effects of FINs alone or in combination with dexamethasone (DXMS) were examined in a mouse model of allergic airway inflammation. Bronchoalveolar lavage fluid and lung tissue were collected to examine airway inflammation.ResultsTreatment with FINs time and dose dependency induced cell death in human and mouse eosinophils. Interestingly, FINs induced non-canonical ferroptosis in eosinophils, which generated morphological characteristics unique to ferroptosis and was iron dependent but was independent of lipid peroxidation. The antioxidants glutathione and N-acetylcysteine significantly attenuated FIN-induced cell death. Treatment with FINs triggered eosinophil death in vivo and eventually relieved eosinophilic airway inflammation in mice. Furthermore, FINs exerted a synergistic effect with DXMS to induce eosinophil death in vitro and to alleviate allergic airway inflammation in vivo.ConclusionsFINs induced ferroptosis-like cell death of eosinophils, suggesting their use as a promising therapeutic strategy for eosinophilic airway inflammation, especially due to the advantage of their synergy with GCs in the treatment of allergic disorders.

Background: Clinical detection of inflammatory markers is useful to assess the degree of nocturnal hypoxia and predict the presence of complications in obstructive sleep apnea syndrome (OSAS) patients. Nowadays, some researchers proposed that hematological parameters could be substituted for novel diseasespecific biochemical markers (such as C-reactive protein) because they were comparatively cheap, simple and practical. But there was a contradiction whether the hematological parameters were positively correlated with the OSAS severity. Methods: Medical databases were searched included PubMed, Web of Science, Scopus, Cochrane Library, Clinical Trial, Embase and Google Scholar (up to March 29, 2018). We used weighted mean differences (WMDs) with 95% confidence intervals (CIs) from random-effects model. Results: Seventeen studies were included in this meta-analysis and results were presented by different hematological parameters. Pooled analysis showed that OSAS was associated with a high level of WBC (white blood cell, 11

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Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis. Intriguingly, the inhibition of mTOR, either by genetic deletion or by another pharmacological inhibitor torin-1, accelerated the eosinophil development in the presence of IL-5. However, this was not observed to have any considerable effect on eosinophil apoptosis. The effect of mTOR in eosinophil differentiation was mediated by Erk signalling. Moreover, myeloid specific knockout of mTOR or Rheb further augmented allergic airway inflammation in mice after allergen exposure. Ablation of mTOR in myeloid cells also resulted in an increased number of eosinophil lineage-committed progenitors (Eops) in allergic mice. Collectively, our data uncovered the differential effects of mTOR in the regulation of eosinophil development, likely due to the distinct functions of mTOR complex 1 or 2, which thus exerts a pivotal implication in eosinophil-associated diseases.