Chemotactic signals released during Burkitt’s lymphoma cell death

Tumour-associated macrophages (TAMs) have been shown to play an important role in tumour survival and progression. Thus, high numbers of macrophages in the tumour tissue are often associated with a poor prognosis. Identification of factors responsible for recruiting macrophages to the sites of different types of tumours might help to develop more effective cancer treatment. Burkitt's lymphoma (BL) is characterised by uncontrolled cell proliferation, high rate of spontaneous apoptosis and significant macrophage infiltration. Although BL cells undergo extensive apoptosis, in situ their corpses are cleared very effectively by macrophages infiltrating the tumour. It is now widely believed that dying cells are themselves able to release chemotactic molecules to ensure macrophage chemotaxis and subsequent clearance of their site of death. Previous work carried out in this laboratory identified fractalkine/CX3CL1 (FKN) released from dying BL cells to be an important player in macrophage chemotaxis to BL. Yet, these results have also indicated that FKN may not be the only chemokine involved in this process. Following from those observations, the first part of this work focused on examination of the potential role of monocyte chemoattractant protein-1 (MCP-1) in macrophage recruitment to BL. Despite the initial promising results, careful analysis of the data obtained by various techniques led to the conclusion that MCP-1 is, probably, not expressed by BL cells. Subsequently, effort was concentrated on understanding mechanisms regulating FKN processing during cell death. The studies performed before in this laboratory identified a new form of FKN to be present in apoptotic BL cells and showed that this is the form that is, most likely, responsible for mediating macrophage migration. Here, this apoptosis-related 60 kDa FKN was found to be a likely caspase-3 cleavage product. Moreover, it was demonstrated that FKN and active caspase-3 are released together in apoptotic BL cell-derived microparticles, suggesting that the proteolytic events could take place also extracellularly. In the final results chapter the differences between BL cell lines in the way they process FKN during cell death were revealed and a new cell death-associated 55 kDa FKN was observed. Through several lines of evidence, this new form was identified to be a possible product of calpain-mediated proteolysis. To conclude, this work provides the first evidence for a possible direct participation of the two major cell death executioner proteases – caspases and calpains, in production of ‘find me’ signals for macrophages and thus, ensuring effective clearance of dying cells. These results indicate that FKN cleavage and release might be of key importance during cell death. Moreover, the studies presented here contribute to better understanding of the process of FKN secretion

Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration

everal lines of evidence suggest that homing of tumor cells to lymphoid tissue contributes to disease progression in chronic lymphocytic leukemia (CLL). Here, we demonstrate that lymph node (LN)-derived CLL cells possess a distinct phenotype, and exhibit enhanced capacity for T-cell activation and superior immune synapse formation when compared with paired peripheral blood (PB) samples. LN-derived CLL cells manifest a proliferative, CXCR4(dim)CD5(bright) phenotype compared with those in the PB and higher expression of T-cell activation molecules including CD80, CD86, and HLA-D-related (DR). In addition, LN-CLL cells have higher expression of α4β1 (CD49d) which, as well as being a co-stimulatory molecule, is required for CLL cells to undergo transendothelial migration (TEM) and enter the proliferation centers of the LNs. Using an in vitro system that models circulation and TEM, we showed that the small population of CLL cells that migrate are CXCR4(dim)CD5(bright) with higher CD49d, CD80, CD86, and HLA-DR compared with those that remain circulating; a phenotype strikingly similar to LN-derived CLL cells. Furthermore, sorted CD49d(hi) CLL cells showed an enhanced capacity to activate T cells compared with CD49d(lo) subpopulations from the same patient. Thus, although PB-CLL cells have a reduced capacity to form immune synapses and activate CD4(+) T cells, this was not the case for LN-CLL cells or those with the propensity to undergo TEM. Taken together, our study suggests that CLL cell immunologic function is not only modulated by microenvironmental interactions but is also a feature of a subpopulation of PB-CLL cells that are primed for lymphoid tissue homing and interaction with T cells

Self-Education in John Paul II's Teaching

Artykuł traktuje o samowychowaniu, jego definicji, warunkach, etapach a także o samopoznaniu, jako jego nieodłącznym elemencie będącym jednocześnie wstępem do aktywności samowychowawczej. Autorka przedstawia w nim stanowisko Jana Pawła II do tej zarówno pedagogicznej, jak i teologicznej kategorii, poprzez którą Bóg nakłada na człowieka obowiązek odkrywania swego powołania, potencjału, jak i samourzeczywistnienia. Cytuje wypowiedzi Papieża Polaka, które świadczą o tym, iż jego zdaniem każdy człowiek powinien wziąć odpowiedzialność za własny ustawiczny rozwój i kształtować w sobie chrześcijańskie cnoty. Artykuł zawiera bogate odniesienia do prac, wypowiedzi Jana Pawła II a także polskich pedagogów i teologów.The article discusses the issue of self-education its definition, conditions and stages, as well as the issue of selfcognition, being and integraf part of it and at the same time an introduction to self-educating activity. The autor presents John Paul II’s standpoint on his pedagogic and theological category, trought which God imposes on the man an obligation of discovering his mission, potential and self-realization. She quotes Polish Pope’s statements, which testify that in his opinion every human being ought to take the responsibility for their own constant development and should shape christian virtues in themselves. The article consist of extensive references to John Paul II’s, Polish pedagogues’ and theologists’ works and statements

The social dimension of Internet fandoms with the ‘Sherlock Polska’ group serving as an example. A research report

W artykule podjęto zagadnienie fandomów internetowych jako społeczności internetowych. Przedstawiono wybrane argumenty na rzecz coraz większej realności zjawisk cyfrowych, zarys problematyki społeczności i fandomów internetowych. Główne problemy badawcze podjęte w tekście dotyczyły następujących kwestii: Czy fandom internetowy, realizowany w grupie Sherlock Polska, sprzyja nawiązywaniu relacji interpersonalnych respondentów? oraz Jaki jest poziom poczucia samotności wśród respondentów? Badania przeprowadzono wśród fanów Sherlocka Holmes’a zrzeszonych w serwisie społecznościowym Facebook za pomocą kwestionariusza ankiety internetowej oraz 11-itemowej Skali Poczucia Samotności De Jong Giervalda (DJGLS); (n = 370).In this paper, the issue of Internet fandoms as an online community is discussed. Selected arguments for an increasing reality of digital phenomena, outline of social issues and Internet fandoms have been presented. The main research questions were: Społeczny wymiar fandomów internetowych na przykładzie grupy Sherlock ‘Is the Internet fandom in the Facebook group ‘Sherlock Polska’ conducive to new interpersonal relationships between interviewees?’ and ‘How common is the feeling of loneliness among the interviewees?’. The research was conducted among Sherlock Holmes’ fans on Facebook by using an online questionnaire and The 11-item De Jong Giervald Loneliness Scale (DJGLS); (n = 370)

The Internet fandom as a friendly space for creators, on the example of the ‘Sherlock Polska’ group. The research report

W artykule podjęto zagadnienie fandomów internetowych jako przyjaznej przestrzeni dla amatorów twórczości fanowskiej. Przedstawiono rys teoretyczny zjawiska fanizmu, założenia metodologiczne badań własnych oraz ich wyniki. Problem badawczy dotyczył odpowiedzi na pytanie: „Czy fandom internetowy realizowany w grupie Sherlock Polska jest przyjazną przestrzenią dla twórców?”. Badania przeprowadzono w maju 2017 r. wśród fanów bohatera literackiego – Sherlocka Holmesa, zrzeszonych w serwisie społecznościowym Facebook za pomocą kwestionariusza internetowej ankiety (n = 370)

Chemotactic signals released during Burkitt's lymphoma cell death

Tumour-associated macrophages (TAMs) have been shown to play an important role in tumour survival and progression. Thus, high numbers of macrophages in the tumour tissue are often associated with a poor prognosis. Identification of factors responsible for recruiting macrophages to the sites of different types of tumours might help to develop more effective cancer treatment. Burkitt's lymphoma (BL) is characterised by uncontrolled cell proliferation, high rate of spontaneous apoptosis and significant macrophage infiltration. Although BL cells undergo extensive apoptosis, in situ their corpses are cleared very effectively by macrophages infiltrating the tumour. It is now widely believed that dying cells are themselves able to release chemotactic molecules to ensure macrophage chemotaxis and subsequent clearance of their site of death. Previous work carried out in this laboratory identified fractalkine/CX3CL1 (FKN) released from dying BL cells to be an important player in macrophage chemotaxis to BL. Yet, these results have also indicated that FKN may not be the only chemokine involved in this process. Following from those observations, the first part of this work focused on examination of the potential role of monocyte chemoattractant protein-1 (MCP-1) in macrophage recruitment to BL. Despite the initial promising results, careful analysis of the data obtained by various techniques led to the conclusion that MCP-1 is, probably, not expressed by BL cells. Subsequently, effort was concentrated on understanding mechanisms regulating FKN processing during cell death. The studies performed before in this laboratory identified a new form of FKN to be present in apoptotic BL cells and showed that this is the form that is, most likely, responsible for mediating macrophage migration. Here, this apoptosis-related 60 kDa FKN was found to be a likely caspase-3 cleavage product. Moreover, it was demonstrated that FKN and active caspase-3 are released together in apoptotic BL cell-derived microparticles, suggesting that the proteolytic events could take place also extracellularly. In the final results chapter the differences between BL cell lines in the way they process FKN during cell death were revealed and a new cell death-associated 55 kDa FKN was observed. Through several lines of evidence, this new form was identified to be a possible product of calpain-mediated proteolysis. To conclude, this work provides the first evidence for a possible direct participation of the two major cell death executioner proteases – caspases and calpains, in production of ‘find me’ signals for macrophages and thus, ensuring effective clearance of dying cells. These results indicate that FKN cleavage and release might be of key importance during cell death. Moreover, the studies presented here contribute to better understanding of the process of FKN secretion.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The architecture of neoplastic follicles in follicular lymphoma; analysis of the relationship between the tumor and follicular helper T-cells

CD4+ T-follicular helper cells are essential for the survival, proliferation, and differentiation of germinal center B-cells and have been implicated in the pathogenesis of follicular lymphoma. To further define the role of these cells in follicular lymphoma, we used multiparameter confocal microscopy to compare the architecture of normal and neoplastic follicles and next generation sequencing to analyze the T-cell receptor repertoire in follicular lymphoma lymph nodes. Multiparameter analysis of lymph nodes showed that the proportion of T-follicular helper cells in normal and neoplastic follicles is the same and that the previously reported increase in T-follicular helper cell numbers in follicular lymphoma is thus due to an increase in the number and not content of follicles. As in normal germinal centers, T-follicular helper cells were shown to have a close spatial correlation with proliferating B-cells in neoplastic follicles, where features of immunological synapse formation were observed. The number of T-follicular helper cells in follicular lymphoma correlate with the rate of B-cell proliferation and T-follicular helper cells co-localized to Activation Induced Cytidine Deaminase expressing proliferating B-cells. T-cell receptor repertoire analysis of follicular lymphoma lymph nodes revealed that follicular areas are significantly more clonal when compared to the rest of the lymph node. These novel findings show that neoplastic follicles and germinal centers share important structural features and provide further evidence that T-follicular helper cells may play a role in driving B-cell proliferation and genomic evolution in follicular lymphoma. Our results also suggest that targeting this interaction would be an attractive therapeutic option