The Essential Role Of Eotaxin And C-C Chemokine Receptor-3 In Allergic Asthma And Its Relationship To The Disorder Of Helper T Cells Subsets

Objective 1 .To explore the effects of airway allergic inflammation (AAI) and eosinophil in bronchial asthma; 2.To explore the effects of Eotaxin and CCR3 receptor by observing expression of Eotaxin and CCR3 mRNA in lung tissue of asthmatic guinea pig, and to study the mechanism of Eotaxin selectively regulating eosinophil; 3.To investigate the changes of T helper cell (TH) subsets and its relationship to Eoaxin, serum total IgE. eosinophil counts and ventilatory function in asthmatic patients. Methods 1 .The ovalbumin (OVA) sensitized and challenged guinea pig model of asthma was adopted ; 2. Bronchial alveolar lavage fluid (BALF) of guinea pigs was acquired, in which the cells were classified and counted; 3. The pathologic samples of lung tissue were stained with HE and were processed for electron microscopy; 4.The expression of ECP in asthmatic airway mucosa was observed by immunohistochemistry (l~ IC); 5.The expression of Eotaxin and CCR3 mRNA in guinea lung tissue was detected by in situ hybridization (ISH), Northern blot and RNA dot blot; 6.The CCR3 gene was detected by reverse transcription polymerase chain reaction (RT-PCR) and the product was cloned and analyzed its sequence; 7.The changes of IFN- æ…½ ~. IL-4~. Eotaxin in peripheral T lymphocyte of asthmatic patients were observed by flow cytometry (FCM) and correlated with serum total IgE, eosinophil count and ventilatory function. Results I .The airway allergic inflammation and the infiltration of eosinophils are the main pathologic changes of asthma; 2. The counts of eosinophils enhanced prominently in BALF of guinea pigs: 3. Electron microscopy shows the epitheliums of bronchial mucosa and alveolus were injured severely and the counts of eosinophils enhanced in pulmonary interstitium, meanwhile eosinophils degranulatd and the charcot-leyden -5- crystals were found; 4.The expression of ECP enhanced and the activated eosinophils increased in lung tissue of asthmatic guinea pig; 5. Eotaxin and CCR3 mRNA were expressed at high levers in Jung tissue of asthmatic guinea pig, which positively corrected with the expression of ECP; 6.The expression of Eotaxin, CCR3 and ECP can be prominently down-regulated by corticosteroid; 7. The sequence of the cloned CCR3 eDNA is coincident with the reported; 8.The balance of IL-4 and IFN- v deviates significantly and relates prominently with Eoaxin, serum total IgE, eosinophil counts and ventilatory function in asthmatic patients. Conclusion 1 .Bronchial asthma is a disease which is characteristic of airway allergic inflammation and infiltration of eosinophils; 2. Eotaxin and CCR3 genes are expressed at high levers in Jung tissue in asthma, which is positively correlated with the expression of eosinophils; 3. The balance of TH subsets deviated significantly is the important mechanism of asthma, meanwhile the cooperative regulation of TH2 cytokines and Eotaxin to eosinophils perhaps is the key step in the pathogenesis of asthma.