Programmed cell clearance

Apoptosis, a physiological process of self-annihilation, is essential during development and for the maintenance of tissue homeostasis. Considerable efforts have been made in recent years to elucidate the molecular mechanisms that govern this mode of cellular demise; however, the subsequent recognition and removal of apoptotic corpses by neighboring phagocytes has received less attention. Nevertheless, macrophage engulfment of apoptotic cells is known to be important in the remodeling of tissues, and contributes to the resolution of inflammation through the removal of effete cells prior to the release of noxious cellular constituents. Moreover, apoptotic cells are a potential source of self-antigens, and clearance of cell corpses is thought to preclude the induction of autoimmune responses. The view is thus emerging that tissue homeostasis is dependent not only on the balance between mitosis and apoptosis, but also on the rate of apoptosis versus that of cell clearance. This review aims to discuss the mechanisms and consequences of macrophage recognition and disposal of apoptotic cells, a process which will be referred to as programmed cell clearance.Received 16 April 2003; received after revision 22 May 2003; accepted 26 May 2003     

Programmed cell death

Programmed cell death     

Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin. More than one-third of MCC patients will die from this cancer, making it twice as lethal as malignant melanoma. Despite the fact that MCC is still a very rare tumor, its incidence is rapidly increasing; the American Cancer Society estimates for 2008 almost 1 500 new cases in the USA. These clinical observations are especially disturbing as the pathogenesis of MCC is not yet fully understood; however, a number of recent reports contribute to a better understanding of its pathogenesis. Here we describe findings regarding the role of Wnt, MAPK and Akt signaling as well as possible aberrations in the p14ARF/p53/RB tumor suppressor network in MCC. Most important, and possibly with high impact on future therapeutic approaches is the demonstration that a polyomavirus has frequently integrated in the genome of the MCC cells prior to tumor development. Received 12 August 2008; received after revision 06 October 2008; accepted 22 October 2008     

Inhibitory effect of direct current on cell division and cell proliferation

Summary Direct current (0.1 to 0.2 mA) fully inhibited cell division and cell proliferation at the site of the non-polarizing anode, probably due to electrolysis and electro-osmotic processes affecting the chromatin of the cell nucleus. It resulted in cessation of the growth of the root-germs of the onion. Plant germs lost their ability to germinate 18–20 h after the application of the weak direct current.     

Inhibition of cell division in mammalian cell cultures by hypertonic medium

Résumé L'arrêt de la métaphase se produit dans les cellules de HeLa S-3 au contact d'un milieu de tonicité accrue (>165 mM). L'accumulation optimale intervient à 277 mM lorsque du NaCl a été utilisé pour augmenter l'influence du milieu. Les effets de l'usage d'autres sels et d'autres types de cellules sont décrits. La dilution du milieu à 165 mM donne lieu à un arrêt synchrone du processus de la mitose dans les cellules et assure la conservation d'un bon synchronisme au cours de la division cellulaire suivante.     

The growth of cell membranes during synchronized cell division ofSaccharomyces cerevisiae

Riassunto Cellule diSaccharomyces cerevisiae venivano coltivate in brodo centenentel-Leucina-³H o³²PO ₄ ^– raccolte in fase log e quindi coltivate in modo sincrono in nuovo terreno privo di radioisotopi. Le cellule e le gemme venivano separate per centrifugazione su gradiente di saccarosio, quindi si isolavano le membrane. La radioattività specifica nelle membrane purificate risultava circa il 50% di quella presente inizialmente nelle cellule usate per la coltura sincronizzata.     

Ras proteins in the control of the cell cycle and cell differentiation

The Ras family of small GTPases includes three closely related proteins: H-, K-, and N-Ras. Ras proteins are involved in the transduction of signals elicited by activated surface receptors, acting as key components by relaying signals downstream through diverse pathways. Mutant, constitutively activated forms of Ras proteins are frequently found in cancer. While constitutive Ras activation induces oncogenic-like transformation in immortalized fibroblasts, it causes growth arrest in primary vertebrate cells. Induction of p53 and cyclin-dependent kinase inhibitors such as p15^INK4b, p16^INK4a, p19^ARF, and p21^WAF1 accounts for this response. Interestingly, while ras has usually been regarded as a transforming oncogene, the analysis of Ras function in most of the cellular systems studied so far indicates that the promotion of differentiation is the most prominent effect of Ras. While in some cell types, particularly muscle, Ras inhibits differentiation, in others such as neuronal, adipocytic, or myeloid cells, Ras induces differentiation, in some cases accompanied by growth arrest. Several possible mechanisms for the pleiotropic effects of Ras in animal cells are discussed. Received 8 March 2000; received after revision 24 May 2000; accepted 24 May 2000     

Proliferation and cell loss of human leukemic cell subpopulations in liquid culture

A kinetic study was performed on leukemic blasts from patients with acute myeloid leukemia, separated into 2 subpopulations by a specific density gradient. The growth curve and the [3H]-thymidine uptake were simultaneously analyzed. While cumulative nucleotide uptake fitted with the growth kinetics in the low-density fraction, such a concordance was not found in the high-density subpopulation. That indicated the occurrence of simultaneous growth and loss in the high density fraction, which could not be evaluated by a simple numerical determination.     

Breaking T cell tolerance to beta cell antigens by merocytic dendritic cells

In type 1 diabetes (T1D), a break in central and peripheral tolerance results in antigen-specific T cells destroying insulin-producing, pancreatic beta cells. Herein, we discuss the critical sub-population of dendritic cells responsible for mediating both the cross-presentation of islet antigen to CD8⁺ T cells and the direct presentation of beta cell antigen to CD4⁺ T cells. These cells, termed merocytic dendritic cells (mcDC), are more numerous in non-obese diabetic (NOD), and antigen-loaded mcDC rescue CD8⁺ T cells from peripheral anergy and deletion, and stimulate islet-reactive CD4⁺ T cells. When purified from the pancreatic lymph nodes of overtly diabetic NOD mice, mcDC can break peripheral T cell tolerance to beta cell antigens in vivo and induce rapid onset T cell-mediated T1D in young NOD mouse. Thus, the mcDC subset appears to represent the long-sought critical antigen-presenting cell responsible for breaking peripheral tolerance to beta cell antigen in vivo.     

Regulation of cell growth

Posters

Regulation of cell growth     

The multifaceted Paneth cell

Paneth cells (PCs) were described over a century ago as granulated cells located at the base of small intestinal crypts, the 'crypts of Lieberkühn.' Various histochemical staining procedures were developed that identified PCs based on their distinctive granule staining pattern. Early on, PCs were proposed to perform a specialized function other than absorption of digested nutrients, the predominant task of the small intestinal epithelium. Since then, many constituents of the PC granules have been biochemically characterized. The presence of various granule-associated antimicrobial substances and their release upon microbial challenge suggest that PCs function as specialized defense cells in the small intestine. Altered resistance to microbial infection in animal models with disrupted or augmented PC function provides further support for the host defense role of PCs. Other PC components suggest that PCs may also participate in the regulation of lumenal ionic composition, crypt development, digestion, and intestinal inflammation. Received 6 June 2001; received after revision 26 July 2001; accepted 27 July 2001     

Peripheral B cell survival

Recent findings suggest that lymphocyte survival is a continuous active process and support the role of B cell receptor engagement in B cell survival. In this context the conflict of survival interests between the diverse B cells gives rise to a pattern of interactions which mimics the behavior of complex ecological systems. In response to competition lymphocytes modify their survival requirements and diverge to occupy different immunological niches through differentiation. Thus naive and memory-activated B cell populations show independent homeostatic regulation. We discuss how niche differentiation allows the coexistence of different cell types and guarantees both repertoire diversity and efficient immune responses.     

Isozymes inDrosophila cell line

Summary Alcohol dehydrogenase, octanol dehydrogenase and fumarase isozyme patterns inDrosophila tissue culture cells were compared with the respective isozyme development pattern in the parental strain. The cell line lacks ADH activity and its fumarase isozyme pattern resembles the pupae and adult type.     

Proliferation and cell loss of human leukemic cell subpopulations in liquid culture

Summary A kinetic study was performed on leukemic blasts from patients with acute myeloid leukemia, separated into 2 subpopulations by a specific density gradient. The growth curve and the [³H]-thymidine uptake were simultaneously analyzed. While cumulative nucleotide uptake fitted with the growth kinetics in the low-density fraction, such a concordance was not found in the high-density subpopulation. That indicated the occurrence of simultaneous growth and loss in the high density fraction, which could not be evaluated by a simple numerical determination.