| Background Goblet cells(GC) in the surface epithelium of the respiratory tract befit first line of defence of the airways. They rapidly secrete mucus to protect the epithelial lining from the battery of dusts microorganisms and other debris delivered by inhalation, a process termed mucociliary clearance. However, as an adjunct to mucociliary clearance, excessive amounts of mucus, leading to mucus trapping and airflow obstruction, thus the protective role of GC mucin secretion becomes pathophysiological and contributes to respiratory diseases such as asthma COPD and cystic fibrosis(CF). Asthma is a chronic inflammatory disease of the bronchial airways, and which is charactered with mucus hypersecretion. Thus, the mucus overproduction increases the degree of airway hyperresponsiveness (AHR) and airflow limitation, contributing to the airway narrowing combination of smooth muscle contraction and airway wall edema, which attends to crucial pathophysiological process of asthma and results in exacerbations and sudden death, Kuyper LM et al provided the evidence that the airway mucus plugging results asthma deaths.Asthma is characterized by a T-helper 2(Th2 )type immune response, BCG is a strong inducer of a T-helper type l(Thl) response, which promotes IfN-γ /IL-12 synthesis and inhibits cytokines from Th2-like cells such as IL-4/ L.-5, airway eosinophilia and AHR to antigens, besides inhibits the GC hyperplasia andmetaplasia(GCH/M) and the mucus secretion. Our previous study also fc md that the phenomena of BCG inhibiting the mucus overproduction in a mouse model of asthma, but haven't studied the mechanisms. The immune system of neonatal and early life is not perfect, which is prone to Th2 type immune response, more recent strategies aim to switch allergen-specific Th2 responses to Thl. Fortunately, some studies show BCG vaccination in early life up-regulated the systemic immune responses and developed a Thl-type response, prevented the development of asthma to some extent. At recent, studies on the mechanisms of BCG vaccination on inhibiting mucus overproduction of asthma are few over the world.Objective Based on a mouse model of asthma we created previously, newborn C57BL/6 mice were vaccinated subcutaneously with BCG early, later sensitized and challenged, then we examine the effects on the airway inflammation and the lung Thl/Th2 cytokines mRNA balance, the effects on airway mucus production, and the changes of MUC5AC mRNA and calcium-activated chloride channel (Gob-5) mRNA in the lung.Methods Newborn C57BL/6 mice (in 24 hours after birth ) were vaccinated with BCG , which were sensitized and challenged by ovabumin (OVA) when they were 6-week-old. First we explored an optimal dose and times of BCG vaccination to suppress airway inflammation, we found subcutaneously injected BCG four times at a lower dose(103 CFU) was effective. Second we assigned newborn mice to three groups: normal saline solution group(group A),asthma model group(group B), BCG-vaccinated group (group C) , and 48 hours after the last challenge, the bronchoalveolar lavage (BALF) inflammatory cell counts, and the pathomorphological changes in the lung were analyzed. The goblet cell hyperplasia ratio (HR) and the epithelial cell mucus occupying ratio (MOR) also measured; The expression of MUC5AC mRNA, Gob-5mRNA and the lung Thl/Th2 cytokines(IL-4N IFN) mRNA in the lung were measured by reverse trancription-polymerase chain reaction( RT-PCR). Results: 1. The effects of BCG vaccination on airway inflammation1.1 the changes of total cells number and EOS in BALFThe total white blood cells in BALF were significantly increased in group B and C compared with group A, but no significant differences between them, while EOS in BALF were decreased significantly (P<0.01)in group C compared with group B.1.2 The effects of BCG vaccination on the changes of pulmonary pathologyIn group A, there are no Eos accumulation around airways and vessels, however there are large amount of inflammatory cells and Eos around airways and vessel...
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