| Objective:To investigate the roles of lung stem cells in airway inflammation associated with intralobar pulmonary sequestration(IPS).This study will provide valuable insights to treat patients with IPS efficiently by developing non-surgical treatments that enhance the repairing capacity of airway epithelium stem cells.Method:Retrospectively analyze the pathologically confirmed clinical cases of IPS to study the epidemiological characteristics,clinical manifestation,imaging features and therapy method by analyzing the medical records.The pathological specimens of IPS were collected.At the same time,four pathological specimens from health people were collected as the health control.We used the HE staining and pulmonary pathological score to analyze the pathological changes of IPS.We also detected the secretion of airway mucin MUC5AC and MUC5B,as well as the number of ciliated cells of IPS using immunofluorescent staining,PAS staining and real-time PCR.The molecular biological and pathological technologies were used to investigate the number,function and proliferation of Type II alveolar epithelial cell(AEC II)in specimen of IPS,which is the stem cell to maintain alveolar epithelium.We also analyzed the gene expression of Type I alveolar epithelial cell.To explore the role of TSP-1 in IPS,we regrouped the pathological specimens of IPS into relative normal portion and obvious lesion portion according to the location.The stereology microscope was used to separate blood vessels from specimens.The gene expressions of TSP-1 were detected in blood vessels.We also detected the existence of bronchioalveolar stem cell(BASC)using immunofluorescent staining and the gene expressions of Club cell using real-time PCR.Results:(1)There were four cases in our study;all of them were IPS at the average age of 25.They were characteristiced by recurrent infections.Only one case was confirmed before operation by CT enhanced scan.All of them were treated by lobectomy with a good prognosis.(2)HE staining and pulmonary pathological score showed obvious changes of IPS.Immunofluorescent staining showed that there were apparently increased secretions of MUC5AC in IPS.And the expression of MUC5AC and MUC5B m RNA were significantly higher in IPS lung than the health control.The number of goblet cells was not significantly changed.The number and expression of ciliated cells was also not significantly changed.(3)The number and expression of SPC were significantly decreased in IPS as compared to the health control.While the SPC~+Ki67~+cell was also reduced obviously in IPS.There were no obvious difference of the gene expressions of AQP5 m RNA and surfactant proteins A,B and D.(4)Compared with the health control,the expression of TSP-1 m RNA was significantly decreased in the relative normal portion of IPS and distinctly increased in the obvious lesion portion of IPS.There are BASCs in human lung tissue.The gene expressions of Club cell was increased in IPS,although difference was not statistically significant.Conclusion:(1)IPS is easily misdiagnosed which should be paid more attention in the clinical.Enhanced CT scan preoperative is useful in diagnosis of IPS and the surgical treatment is the best choice.(2)There are obviously pathological changes in IPS.Secretory hyperresponsiveness and pulmonary mucus hypersecretion may be an important reason for the recurrent infections of IPS.Inhibition of mucus hypersecretion may be a new way for treatment of IPS.(3)The significant changes of AEC II numbers and proliferation capacities in IPS may result in relevant reduction of lung regeneration capacities.(4)TSP-1 may regulate the differentiation of BASC and further affect the lung regeneration capacities.In conclusion,IPS is a chronic infection disease and is characteristic by recurrent infection.The mucociliary clearance is damaged and AEC II is significantly changed.The numbers and proliferation capacities of pulmonary stem cells/progenitor cells may be regulated by TSP-1 secteted by endothelial cells. |
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