Mucociliary clearance is the primary physical mechanism to protect the human airways against harmful effects of inhaled particles. Environmental factors play a significant role in the impairment of this defense mechanism, whereas cigarette smoke is discussed to be one of the clinically most important causes. Impaired mucociliary clearance in smokers has been connected to changes in ciliated cells such as decreased numbers, altered structure and beat frequency. Clinical studies have shown that cilia length is reduced in healthy smokers and that long-term exposure to cigarette smoke leads to reduced numbers of ciliated cells in mice. We present an in vitro model of primary normal human bronchiolar epithelial (NHBE) cells with in vivo like morphology to study the influence of cigarette mainstream smoke on ciliated cells. We exposed mucociliary differentiated cultures repeatedly to non-toxic concentrations of mainstream cigarette smoke (4 cigarettes, 5 days/week, 8 repetitions in total) at the air-liquid interface. Charcoal filter tipped cigarettes were compared to those being equipped with standard cellulose acetate filters. Histopathological analyses of the exposed cultures showed a reduction of cilia bearing cells, shortening of existing cilia and finally disappearance of all cilia in cigarette smoke exposed cells. In cultures exposed to charcoal filtered cigarette smoke, little changes in cilia length were seen after four exposure repetitions, but those effects were reversed after a two day recovery period. Those differences indicate that volatile organic compounds, being removed by the charcoal filter tip, affect primary bronchiolar epithelial cells concerning their cilia formation and function comparable with the in vivo situation. In conclusion, our in vitro model presents a valuable tool to study air-borne ciliatoxic compounds.
Parenchymal (epithelial or mesenchyma) stem cells are rapidly drawing both scientific and clinical attention in solid organs like the liver, skin, intestine and abdominal mesothelium, just as has been the case in the hematopoietic system. For the stem cells of these organs various definitions, markers for identification, methods of isolation and in vitro cultivation, and lineage mechanisms have been proposed and some of them are now proven to be valid and useful. In this article attempts will be made to explore whether there are stem cells in the lower respiratory system (from the trachea to the lung periphery) and what they look like. Because of its anatomical and functional complexity the stem cell concept for the respiratory system has been developing rather slowly. Nevertheless, the data available seem to indicate that in analogy to the above mentioned organs there is only one type of epithelial stem cells throughout all sections of the lower respiratory system during fetal through adult stages. They are multipotent for cell differentiation and able to yield lineage progenitors for ciliated, goblet, basal. Clara neuroendocrine, alveolar type 1 and alveolar type 2 cells.
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