| The overall pathogenic view of respiratory allergy has changed and evolved substantially in recent years. The concept of minimal persistent inflammation (MPI) marks the beginning of a new field in allergic inflammation and it makes the optimal therapeutic strategy for allergic reaction (AR) focus on minimizing inflammatory phenomena rather than only alleviating acute symptoms. Recent clinical studies indicate even when exposure to allergen (pollen or dust mites) is too low to provoke symptoms, there is still inflammatory infiltration in the nasal mucosa of the allergic patients. MPI is characterized by a mild infiltration of inflammatory cells (i.e., eosinophils) at the site of the allergic reaction and weak intercellular adhesion molecule-1 (ICAM-1) expression on epithelial cells in asymptomatic allergic subjects. MPI is specific to ongoing allergic disease. When the allergenic stimulus is prolonged, as happens during a natural exposure, this inflammation becomes chronic and persistent. Chronic inflammation is one of the most important factors which induce airway remodeling (RM). It has been proved that changes of nasal mucosa during remodeling include epithelial shedding, thickening of the basement membrane, mucous gland and goblet cell hyperplasia, and increased collagen deposition. It is known that changes during RM will make the disease more serious and more difficult to cure. So, in this study, we investigated that whether long time MPI in allergic rhinitis resulted in some feature of remodeling in nasal mucosa or not and what factors played an important role in the disease progression.Part 1 Establishment of MPI Models in Allergic Rhinitis Guinea PigsAn animal model of MPI was developed by repeated local booster sensitization with different concentration of physiological saline containing ovalbumin into the nasal cavity of sensitized guinea pigs. Hematoxylin and eosin (H&E) stain were used to detect EOS and immunofluorescence under the laser scanning confocal microscope was performed to determine ICAM-1 protein. The criterion of successful MPI models were assessed by the symptoms (sneezing and nasal rubbing) after antigen challenge, the infiltration of eosinophils (EOS) and the expression of intercellular adhesion molecule 1(ICAM-1) in the nasal epithelial cells.Our results showed that the symptoms, infiltration of EOS and the expression of ICAM-1 varied significantly with the concentration of OVA suspension. So, we have successfully established MPI models in the sensitized guinea pigs which will provide us with a new method for further research.Part 2 Changes in nasal mucosa of MPI ModelsThe following experiment is to examine the changes of nasal mucosa in MPI models. Furthermore, the expression of TGF-β1 (transforming growth factor-β1, TGF-β1) and MMP-9 (matrix metalloproteinases-9,MMP-9) were also investigated here. Methods of alcian blue-periodic acid-Schiff (AB-PAS) and Masson's Trichrome (MT) were used to determine the number of goblet cells and the percentage of MT stained area within the basement membrane of epithelium. The expression and distribution of TGF-β1 and MMP-9 in nasal mucosa were estimated by double immunofluorence under a confocal laser scan microscopy system. Compared with the control group, the increased goblet cells (t=13.720, p<0.05) in nasal epithelium together with the increased collagen fibrils (t=4.542, P<0.05) within the basement membrane of epithelium were observed in the MPI model group. Besides, there is nearly no expression of TGF-β1 in the control group and the expression of MMP-9 was mildly found only in the epithelium cell. In contrast, there was significantly higher expression of TGF-β1 and MMP-9 (t=25.218, p<0.05) in nasal mucosa of MPI model group than that in control group. TGF-β1 mainly expressed in the epithelium cell, the infiltrated inflammatory cell and extracellular matrix, while MMP-9 expressed in the epithelium cell and the infiltrated inflammatory cell.ConclusionIn summary, we have successfully established MPI models in the sensitized guinea pigs and have demonstrated that some characters of remodeling may also exist in the nasal mucosa of MPI models, which would bring us a new thinking for the importance of MPI in the progression of allergic diseases. The global strategy of allergy treatment should be modified to long-term treatment throughout the entire period of allergenic exposure and early intervention to avoid remodeling in nasal mucosa is of the most importance. |
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