| Background: Innate immunity has been thought to be involved in asthma pathogenesis.Pentraxins,acting as soluble pattern recognition molecules,play an important role in humoral innate immunity.Asthma is a heterogeneous inflammatory disease of airways and can be classified as eosinophilic or non-eosinophilic asthma.Objective: To investigate whether pentraxin levels differ in subjects with eosinophilic versus non-eosinophilic asthma.Furthermore,to access the predictive performance of pentraxin levels for discriminating asthma inflammatory phenotypes.Methods: A total of 80 asthmatic patients and 24 healthy control subjects underwent sputum induction at study inclusion.Differential leucocyte counts were performed on selected sputum.Plasma C-reactive protein(CRP),serum amyloid P(SAP),pentraxin 3(PTX3),and sputum SAP,PTX3,IL-8 levels were determined by enzyme-linked immunosorbent assay.Results: Subjects with non-eosinophilic asthma had significantly increased pentraxin levels compared with those with eosinophilic asthma and healthy controls,with median(interquartile range)plasma CRP levels of 0.86 (0.28-2.07),0.26(0.14-0.85),and 0.15(0.09-0.45)mg/L(P <.001),respectively,plasma SAP levels of 33.69(19.79-58.39),19.76(16.11-30.58),and 20.06(15.68-31.11)mg/L(P =.003),respectively,and sputum PTX3 levels of 4.9(1.35-18.72),0.87(0.30-2.07),and 1.08(0.31-4.32)ng/m L(P <.001),respectively.Conversely,sputum SAP concentrations of eosinophilic asthmatics(median,21.49 ng/m L;IQR,6.86-38.79 ng/m L)were significantly higher than those of non-eosinophilic patients(median,8.15 ng/m L;IQR,2.82-18.01 ng/m L)and healthy controls(median,8.79 ng/m L;IQR,2.00-16.18 ng/m L).Asthma patients with high plasma CRP(P =.004),SAP(P =.005)and sputum PTX3 levels(P < 0.001)also had significantly lower sputum eosinophil percentages.Sputum PTX3 levels had the best power(11.18-fold,P <.001)to predict non-eosinophilic airway inflammation in asthma patients.Conclusion: Pentraxin levels differed significantly between patients with non-eosinophilic asthma and those with eosinophilic asthma.Furthermore,elevated pentraxin expressions may predict non-eosinophilic airway inflammation in asthmatic patients.Background:Pentraxin 3(PTX3)play an important role in humoral innate immunity.Recently,it has been reported that PTX3 deficiency enhances IL-17A–dominant pulmonary inflammation in an ovalbumin-induced mouse asthma model.Objective:To investigate the effect of exogenous PTX3 on the phenotype of bronchial asthma.Methods:C57BL/6J mice were sensitized and challenged with OVA to induce eosinophilic asthma model,as well as sensitized with ovalbumin(OVA)plus LPS and challenged with OVA to induce neutrophilic asthma model.We evaluated effect of recombinant PTX3 on asthma phenotype through both asthma models.The bronchoalveolar lavage fluid(BALF)inflammatory cells and cytokines,airway hyperresponsiveness,and pathological alterations of the lung tissues were assessed.Results:In both eosinophilic and neutrophilic asthma model,recombinant PTX3 enhanced airway hyperresponsiveness,production of inflammatory cytokines IL-4,IL-17 and eotaxin,and airway accumulation of inflammatory cells,especially eosinophils and neutrophils.In histological analysis of the lung tissue,administration of PTX3 promoted inflammatory cell infiltration into lung tissue and mucus production in airway goblet cells.In addition,PTX3 also significantly upregulated the BALF level of TGFβ1,one of the main mediators involved in tissue remodeling in the asthmatic airway,and enhanced Stat3 pathway activity in lung tissue.Conclusion:Our results show that exogenous PTX3 can exacerbate multiple asthmatic features by promoting both eosinophil and neutrophil lung infiltration and provide new evidence to better understand the complex role of PTX3 in asthma pathogenesis. |
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