| Background: Asthma is a chronic inflammatory disorder of the airways in which many cells and cytokines participate associated with variable airflow limitation, airway mucus hytersecretion and airway hyperresponsiveness(AHR).Increasing evidence suggests that eosinophil(Eos) play a central role in the pathogenesis of asthma and there is even a designation of "Eosinophil Inflammation". Many a study provide evidence that allergen challenge induces Eos migration from bone marrow (BM) through peripheral blood to the airways in sensitized mice so that verdict "asthma derived from BM" is established. But it is not completely clarified of the mechanism of Eos migration. It has been documented that many cytokines and chemotaxins regulate the course of Eos migration in which interleukin-5(IL-5) and eotaxin are the key mediator. IL-5 is considered as an essential mediator in Eos migration from BM and Eos differentiation, proliferation and activation. In the transgenic murine model of asthma, the overexpression of IL-5 induces eosinophilia in peripheral blood and the airways. As a specific chemotaxin of Eos, eotaxin has a hyperselective attraction to Eos. Many a study indicate that eotaxin can induce eosinophil recruitment in tissue. But there is few evidence about the interaction of IL-5 and eotaxin. More and more interests have been attached on the immunological treatment of asthma in particularly inhibiting Eos migration via blocking the effect of IL-5 and eotaxin. Hypothesis: Allergen challenge induced the regular migration of Eos from BM through peripheral blood to the airways as well as proliferation of Eos progenitor in BM. These changes are associated with the local and/or circulating production of eosinopoietic signal-IL-5 and local production of eosinophil chemotactic signal-eotaxin. We suppose that anti-IL-5 monoclony antibody (TRFK-5) could inhabit the migration of Eos from BM to the airways. Meanwhile, based on the conclusion of eotaxin on the attract of Eos, we suppose that combination of TRFK-5 and eotaxin couldn't establish pulmonary eosinophilia, which indicates that the eotaxin chemotactic effect on Eos must depend on the collaboration of IL-5. hi order to investigate this hypothesis, a murine model of asthma was used. Methods:Male C57BL/6 mice (6-8wk of age) were sensitized twice andchallenged thrice by ovalbumin(OVA) as OVA/OVA group, and mice were treated by normal saline as SHAM/SHAM group. The outcome measurements include white blood cell (WBC) total count and differential count of bronchoalveolar lavage fluid (HALF) and peripheral blood (PB), nucleate cell count and eosinophil percentage of BM. These parameters were collected 48h after the final allergen challenge. To show Eos infiltration, the histology of lung tissues was also observed. Further, the effects of intranasal TRFK-5(50Dg/mouse, 2h before OVA challenge, for 4 days), combination of TRFK-5(50Dg/mouse, 2h before OVA challenge, for 4 days) and eotaxin(4Dg/mouse,6h after the final challenge) on above changes were investigated. Results:Eosinophil numbers of BALF, PB and BM increase considerably 48h after final OVA challenge compared with negative group, (34.89 ?8.59 x 104 (32.75%) vs 0.07 ?0.10 x 104 (0.20%) (p<0.01), 205.15 ?16.1 x loVml (3.20%) vs 41.06 ?42.99 x I03/ml (1.10%) (p<0.05^ 1.25 ?0.08 x 106/femur (5.45%) vs 0.59 ?.17xl06/femur(2.9%)(p<0.05)respectively).The histology of lung tissues showed that the infiltration of Eos has significantly high density compared with N.S control group. Intranasal TRFK-5, 50Dg/mouse, 2h before OVA challenge, for 4 days, decrease the eosinophil numbers of BALF, PB and BM in OVA/OVA group mice(0.74?.35xl04(0.95%) (PO.OlvsOVA group),30.47?3.73xl03/ml(0.90%)(P<0.05vsOVA group),0.49?.04xl06/femur ( 2.70% ) (PO.05 vsOVA/OVA group) respectively). The histology of lung tissues showed that no Eos infiltration. Combinational intranasal TRFK-5 and eotaxin (40g/mouse,6h after the final challenge) can't established eosinophilia of BALF, PB and BM in OVA/OVA group mice(0.99?.19x!04 ( 1.0% ) (P<0.01... |
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