The PtdIns 3-Kinase/Akt Pathway Regulates Macrophage-Mediated ADCC against B Cell Lymphoma

Macrophages are important effectors in the clearance of antibody-coated tumor cells. However, the signaling pathways that regulate macrophage-induced ADCC are poorly defined. To understand the regulation of macrophage-mediated ADCC, we used human B cell lymphoma coated with Rituximab as the tumor target and murine macrophages primed with IFNγ as the effectors. Our data demonstrate that the PtdIns 3-kinase/Akt pathway is activated during macrophage-induced ADCC and that the inhibition of PtdIns 3-kinase results in the inhibition of macrophage-mediated cytotoxicity. Interestingly, downstream of PtdIns 3-kinase, expression of constitutively active Akt (Myr-Akt) in macrophages significantly enhanced their ability to mediate ADCC. Further analysis revealed that in this model, macrophage-mediated ADCC is dependent upon the release of nitric oxide (NO). However, the PtdIns 3-kinase/Akt pathway does not appear to regulate NO production. An examination of the role of the PtdIns 3-kinase/Akt pathway in regulating conjugate formation indicated that macrophages treated with an inhibitor of PtdIns 3-kinase fail to polarize the cytoskeleton at the synapse and show a significant reduction in the number of conjugates formed with tumor targets. Further, inhibition of PtdIns 3-kinase also reduced macrophage spreading on Rituximab-coated surfaces. On the other hand, Myr-Akt expressing macrophages displayed a significantly greater ability to form conjugates with tumor cells. Taken together, these findings illustrate that the PtdIns 3-kinase/Akt pathway plays a critical role in macrophage ADCC through its influence on conjugate formation between macrophages and antibody-coated tumor cells

Thinking through science. 1

Cumple con los requisitos del currículo nacional inglés para la etapa 3 de secundaria (Key stage 3). Además de los conocimientos exigidos a los alumnos para esta etapa escolar y su comprensión, se pretende desarrollar en ellos las habilidades mentales que están relacionadas con la práctica de las ciencias.SCBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 planta; 28014 Madrid; Tel. +34917748000; [email protected]

Thinking through science. 2

Cumple con los requisitos del currículo nacional inglés para la etapa 3 de secundaria (Key stage 3). Además de los conocimientos exigidos a los alumnos para esta etapa escolar y su comprensión, se pretende desarrollar en ellos las habilidades mentales necesarias que están relacionadas con la práctica de las ciencias.SCBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 planta; 28014 Madrid; Tel. +34917748000; [email protected]

Leadership: Native Narratives on Building Strong Communities

Indigenous scholars strive to produce accessible research grounded in the daily lives of Native peoples, research that will improve their communities in meaningful and sustained ways. They also recognize that long-lasting change depends on effective leadership. Living Indigenous Leadership showcases innovative research and leadership practices from diverse nations and tribes in Canada, the United States, and New Zealand. The contributors, all women, use vibrant stories and personal narratives to offer insights into the unique nature of Indigenous leadership. --Publisher\u27s website. Dr. Carolyn Kenny is a professor of Human Development and Indigenous Studies in the PhD Program in Leadership & Change at Antioch University. Students and graduates of the PhD Program in Leadership & Change have contributed chapters in this book: Raquel D. Gutierrez, Gail Cheney, Annette Squetimkin-Anquoe, Michelle Archuletta Link to Table of Contentshttps://aura.antioch.edu/facbooks/1004/thumbnail.jp