Background The intracellular bacterium Chlamydia pneumoniae is suspected to play a role in formation and progression of atherosclerosis. pneumoniae infected cells. Ultrastructure of Chlamydia pneumoniae infected human aortic easy muscle mass cells showed considerable membrane- and organelle damage, chromatin condensation but no nuclear fragmentation. DNA fragmentation as well as cell membrane permeability was analyzed by TUNEL and NHS-biotin staining and occurred exclusively in cells transporting Chlamydia pneumoniae spots but not in easy muscle mass cells with inclusions. These morphological features of cell death were not accompanied by an activation of caspase-3 as revealed by analysis of enzyme activity but involved mitochondrial membrane depolarization as shown by TMRE uptake and release of Rabbit Polyclonal to SLC6A1 cytochrome c from 6199-67-3 manufacture mitochondria. Conclusion This study provides evidence that Chlamydia pneumoniae induce a spot like contamination in human aortic easy muscle mass cells, which results in a chimeric cell death with both 6199-67-3 manufacture apoptotic and necrotic characteristics. This aponecrotic cell death may aid chronic inflammation in atherosclerotic blood vessels. Background Contamination with Chlamydia pneumoniae (Cpn) usually causes acute respiratory tract infections [1]. Chronical contamination with Cpn may also contribute to formation and progression of atherosclerotic lesions apart from the classical risk factors such as hypertension, hypercholesterolemia and hyperlipidemia [2]. Cpn has been extensively analyzed in the context of atherosclerosis [3] because atherosclerosis and cardiovascular disease are the leading causes of death in the United Says, Europe and much of Asia [4,5]. The obligate intracellular bacterium has been detected in atherosclerotic lesions by immunohistochemistry, polymerase chain reaction and electron microscopy [6-8] and has also been cultured from atheromatous plaques [9,10]. On the cellular level easy muscle mass cells and macrophages in the intima have been found to be infected with Cpn [11,12]. In general terms, if the inflammatory response does not effectively neutralize or remove the offending brokers, such as Cpn, it can continue indefinitely producing in the progression of the disease [2]. Chlamydiae exhibit a unique developmental cycle with two morphological unique infectious and reproductive forms: the elementary- and the reticulate body. The life cycle profits for 48 C 72 h and ends with pathogen release that may damage the host cells [13]. Contamination with this pathogen is usually accompanied by cytoplasmic modifications and damage of the host cells [12]. A balance between pro- and anti-apoptotic influences by Chlamydia can be postulated. On one hand it has been shown that Chlamydia psittaci and Chlamydia trachomatis can induce apoptosis in vitro [14,15]. On the other hand established cell lines infected with Cpn or Chlamydia trachomatis were guarded from apoptotic cell death induced by numerous stimuli [16,17]. Most of the studies looking into pro- and anti-apoptotic activity of Cpn were performed in tumor cells or established cell lines. Since the character of cell death is usually affected by host cell type and Chlamydia strain it is usually of relevance to determine cell death in Chlamydia infected main cells [18]. As regards the role of Cpn in atherosclerosis we need to understand death promoting and inhibiting capacities of Cpn in main cultures of vascular cells. 6199-67-3 manufacture Human aortic easy muscle mass cells (HASMC) play an important role in the development of atherosclerotic lesions [19]. Therefore, we sought to clarify the nature of cell death induced by Cpn in HASMC. Apoptosis and necrosis represent two extreme morphologically defined forms of cell death [20-23]. Recently the cross term aponecrosis was launched describing the incomplete performance of the internal apoptotic pathway and the following necrotic degeneration [24]. Whether easy muscle mass cell death is usually apoptotic, necrotic or even aponecrotic in nature would predictably influence the inflammatory response in the plaque..