The Mechanism Of HDM Through The Alveolar Macrophage TLR4-induced Airway Inflammation In Asthmatic Mice

Objectives:Bronchial asthma is a disease characterized by chronic airway inflammation, many inflammatory cells and inflammatory factors contributed to its development. "Hygiene hypothesis" can only partially explain the increasing incidence rate of asthma. Asthma is the result of both heredity and environment (in other words, inherent immunity and acquired immunity). Research on the interactions between these two immune systems will provide more conclusive information on the etiology and mechanism of asthma.Nowadays, researchers are paying more and more attention on the contribution of house dust mite, endotoxin, viral infection to asthma. House dust mite(HDM) is an important part of pathogen in the surrounding environment, we treat the asthma mouse model with the HDM. We intend to investigate the activation of TLR4 by HDM, and then the activation of AM by TLR4. We aim at confirming the airway inflammation caused by AM activation, so as to identify the etiology and mechanism of asthma.Methods:30 female BALB/c mice were randomly divided into OVA group (A), HDM+OVA group (B) and control group (C). We used OVA sensitization and challenge to induce a murine asthmatic model. HE stain was used to monitor the pathological changes of airway and lung. The optical microscope was used to observe the cells from BALF; The concentration of IL-4,L-5,L-13 and IFN-γwas determined by ELISA; The expression of AM and TLR4 was measured by Real-time PCR; The expression of CD80 and CD86 was detected by FCM.Results:1. In group A, bronchus sub-mucosa edema, mucus gland hyperplasia, eosinophile granulocyte dominated inflammatory cells infiltration among all layers; In group B, breakage of interalveolar septum, lung interstitium congestion, neutrophile granulocyte and leukomonocyte dominated inflammatory cells infiltration in the alveolar space; In group C, no airway endepidermis hyperplasia, no inflammatory cells infiltration, intact alveolar wall.2. The total cell count, neutrophile granulocyte count of group B was significantly higher than group A, but the eosinophile granulocyte count was similar.3. The concentration of IL-4, IL-5, IL-13 and IFN-y in BALF of group A was significantly higher than group C, the concentration of IL-4, IL-5 and IL-13 in BALF of group B was significantly higher than group A, the concentration of IFN-γwas similar.4. The expression of AM and TLR4 mRNA in group B was statistically higher than group A, while group A and C was similar.5. The expression of CD86 of group B was significantly higher than Group A, the CD80 expression was similar.Conclusions:HDM will activate the AM through TLR4 passway so as to accelerate the airway inflammation.