Some cases showed a dose dependent increase of acti vated caspase 3. There has also been evidence for caspase independent apoptosis in CSE treated cells, as shown with the use of caspase inhibitors. Other groups concluded that necrosis the following site was the only out come following CSE treatment of A549, Jurkat and human umbilical vein cells, or human primary and. These chemicals are in turn diluted in the existing air volume in the airways so that the resulting toxicity is not instantly detrimental for the epithelium, or the tissues surrounding it. Instead, chronic smoking results in the well documented loss of the lung internal structures, which is due to the accumulation of toxic insults, increased epithelial cell death and a decline in immune cell Inhibitors,Modulators,Libraries function.

Exposure of cells to CS by means of CSC or CSE Inhibitors,Modulators,Libraries does not provide a reliable simulation system of normal smoking. In human lungs, the inhaled tobacco smoke is extensively diluted due to the huge volume of air inhaled after each puff. This dilution Inhibitors,Modulators,Libraries of the CS prevents the acute accumulation of a toxic criti cal mass and the ensuing cell damage, which more than likely happens when either CSC or CSE is used to chal lenge cultured cells. Furthermore, using either of these methods, it is very difficult to determine the quantity and the quality of the supplied dose and its toxicity. To our knowledge, there has never been in the literature a system atic and quantitative analysis of the tobacco components present in such a preparation. Therefore, it is plausible that only the water soluble components of CS and a small part of the particulate matter contribute to the toxicity of these preparations.

According to our method, the toxic substances Inhibitors,Modulators,Libraries in the gaseous phase of CS that are supplied to cells are diluted in a measured air volume within the vol umetric chamber so that their contact with the cells simu lates normal smoking conditions. In addition, each dose of the GPS supplied has previously been tested for its toxic component load using a well established method. Previous research mainly focused on the effect of CS on airway epithelium cells, since they are the first cell lineage directly exposed to the toxic effects of tobacco smoke. Smoking, however, triggers inflammation of the airways, which is brought about Inhibitors,Modulators,Libraries by a cascade of events attributed to both innate and BAY 73-4506 acquired immune reactions. It is therefore of interest to study the immediate effect of CS on immune cells, as they have the ability to both initiate and perpetuate inflammatory responses in the diseased lung. To date, there are several accounts in the literature that report impaired responsiveness of immune cells mainly T cells in murine models that have been attributed to mainstream tobacco smoke.