Apoptotic effects of tamoxifen on leukocytes from horse peripheral blood and bronchoalveolar lavage fluid

A reduction in inflammatory cell apoptosis is an important concept in the maintenance of inflammation and a potential target for the resolution of inflammation in many inflammatory diseases. Dysregulation of apoptosis has been implicated in a range of diseases, including tumors, neurodegenerative disorders and autoimmunity, and may also be implicated in allergic asthma. In horses, recurrent airway obstruction (RAO) is an asthma-like condition that is characterized increased survival neutrophil bronchial. Tamoxifen is a synthetic, non-steroidal, anti-estrogen agent that is widely used for treating all stages of breast cancer and has been approved for the prevention of breast cancer in high-risk women. The observed efficacy of tamoxifen has been attributed to both growth arrest and the induction of apoptosis. Therefore, the aim of our study was to evaluate the ability of tamoxifen to induce apoptosis in vitro in granulocytic cells from peripheral blood and in mononuclear cells from bronchoalveolar lavage fluid (BALF) in horses. Flow cytometry using commercial AnnexinV-FITC and propidium iodide was used to quantify early and late apoptotic leukocytes, respectively. The results showed a significant increase in early apoptosis in peripheral blood and bronchial granulocytic cells treated with tamoxifen. The rate of early apoptosis of mononuclear cells from blood and BALF when incubated with tamoxifen was significantly lower compared with granulocytic cells. We did not observe a direct effect of tamoxifen on late apoptosis in any of the in vitro assays in the cell types used here. These results indicate that the apoptotic mechanisms under these experimental conditions would affect only blood and BALF granulocytic cells, particularly in early apoptosis. Finally, further in vitro and in vivo studies are needed to better understand apoptotic mechanisms because tamoxifen could be used to treat chronic, inflammatory pathologies associated with granulocytes and allergic diseases, such as asthma or equine RAO.