Study On Regulatory Mechanism Of Macrophage Inflammatory Reaction In Chronic Obstructive Pulmonary Disease Treated With Aspergillus Fumigatus Infection

The Relationship of Macrophage Function with Receptor Expression in Patients with Chronic Obstructive PulmonaryTo study airway macrophages function changes and its relationship with receptor expression in patients with COPD.84 patients with COPD in our hospital between January2015 and March 2016 were divided into the mild-moderate group(44 cases)and the severe group(40 cases),and selected 40 healthy people as the control group.We obtained the induced sputum from the three groups,separated macrophage,and detected the phagocytic index(PI)of fluorescent taged aspergillus spores.Real-time quantitative reverse transcription PCR method was used to detect the expression of related genes of 3groups.Results: The total number of cells in mild-to-moderate group and severe group were more than in the control group,but the macrophages ratio had dropped significantly(P<0.05).All the phagocytosis of macrophage were restrained in mild-to-moderate group and severe group.PI of three groups had statistically significant difference(P<0.05).The difference in expression quantity of Macrophage SR with collagenous structure(MARCO)and Scavenger receptor-A1(SR-A1)had no statistical significance between the three groups(P>0.05).Toll-like receptors-4(TLR4)expression quantity in mild-to-moderate group showed no statistically significant difference,when compared with control group,but that in severe group was upregulated and had significant difference with those of the mild-to-moderate group and the control group(P<0.05).MUC5 A and AQP5 expression quantity also showed statistically significant differences between three groups(P<0.05).Macrophages PI was negatively correlated with the expression quantity of TLR4 and MUC5A(P<0.05),but positively correlated with the expression quantity of AQP5(P<0.05).Patients with COPD had the proportion of macrophages decreased and the phagocytosis function restrained as more greatly as the disease was aggravating.Its mechanism may be related to the up-regulation of TLR4 and MUC5 A expression and down-regulation of AQP5 expression.HMGB1 Mediates Aspergillus fumigatus-induced Inflammatory Response in Alveolar Macrophages of COPD MiceChronic obstructive pulmonary disease(COPD)is a chronic inflammatory disease and the incidence and mortality of Aspergillus fumigatus(A.fumigatus)infected COPD patients increasing in recent years.HMGB1,which could mediate various extracellular inflammatory responses,increased in COPD patients.The aim of this study was to investigate the role and mechanism of HMGB1 in A.fumigatus infected alveolar macrophages of COPD mice.In this study,COPD mice were established by cigarette smoking and the pathological changes in the lung tissues were detected by HE staining.The alveolar macrophages isolated from the bronchoalveolar lavage fluid were infected with A.fumigatus conidia and then the expression of HMGB1 was assayed by Real-time PCR and Western blot.The levels of pro-inflammatory cytokines(TNF-?,IL-1?,IL-6 and IL-33),which was confirmed by TLR2/4 or Dectin-1 siRNA,RAGE,Dectin-1,and TLR2/4 were assayed after knockdown of HMGB1 in A.fumigatus infected alveolar macrophages of COPD mice.We also explored the effects of HMGB1 on MyD88/NF-?B and syk/PI3 K signaling pathways.HMGB1 expression was significantly increased in the alveolar macrophages of COPD mice after infection with A.fumigatus.The pro-inflammatory cytokine expression was remarkably reduced by HMGB1,TLR2/4 or Dectin-1 siRNA.The levels of Dectin-1 and TLR2/4,but not RAGE were decreased by HMGB1 siRNA.Furthermore,the expression of MyD88,p-p65,p-syk,and PI3 K was decreased and I?B increased by HMGB1 siRNA.In conclusion,HMGB1 is responsible for A.fumigatus-induced inflammatory response in COPD alveolar macrophage via Dectin-1and TLR2/4 receptor through activating MyD88/NF-?B and syk/PI3 K signaling.