Search PubMed⌕ Search

Biomedical subjects

Osnat Bohana-Kashtan

Publications and source records attributed to Osnat Bohana-Kashtan.

5 recordsLinked to original sources
PubMed2006

Ex vivo soluble fas ligand treatment of donor cells to selectively reduce murine acute graft versus host disease.

BACKGROUND: Allogeneic bone marrow transplantation (BMT) and donor lymphocyte infusion (DLI) provide valuable treatments for a range of diseases. However, the therapeutic utility of BMT and DLI is reduced by the high incidence of graft-versus-host disease (GvHD) mediated by activated donor T lymphocytes directed against recipient alloantigens. METHODS: Using mouse models, we developed and evaluated a strategy to selectively enhance activation-induced cell death (AICD) of anti-recipient T cells within transplant donor cell populations, with the goal of reducing GvHD. Responder T lymphocytes were incubated ex vivo with irradiated allogenic stimulator cells in a mixed lymphocyte reaction (MLR) in the presence of soluble Fas ligand (sFasL) to induce AICD in alloreactive cells. RESULTS: This ex vivo sFasL treatment reduced proliferation to the allogeneic stimulator cells in vitro and abrogated acute GvHD capacity in vivo. In contrast, the secondary immune responsiveness of the ex vivo sFasL-treated responder T cells to an unrelated model antigen was preserved. Furthermore, upon adoptive transfer in a DLI model, ex vivo sFasL-treated T cells were able to reject a model tumor. Finally, ex vivo sFasL treatment of bone marrow cells did not reduce their hematopoietic engraftment capacity. CONCLUSIONS: Thus, ex vivo treatment with sFasL appears to have potential for translation to clinical cell processing of BMT allografts and DLI infusions.

Acute Disease↗
PubMed2005

Extracellular phosphorylation of C9 by protein kinase CK2 regulates complement-mediated lysis.

Ecto-protein kinases (ecto-PK) are expressed on many cell types, both normal and malignant, yet their functions are largely unknown. An ecto-PK capable of phosphorylating the C9 component of the complement system is described. This C9 ecto-PK could be inhibited by TBB, Emodin and DRB, selective inhibitors of protein kinase CK2. Treatment of Raji human B lymphoma cells with these CK2 inhibitors augmented cell killing by Rituximab (anti-CD20 antibodies) and human complement. Analysis of C5b-7-bearing Raji cells showed that extracellular inhibition of the ecto-CK2 enhanced cell lysis by C8 and C9. Blocking of the membrane complement regulator CD59 with monoclonal antibodies further enhanced the effect of the CK2 inhibitors on Raji cell death by complement. C9 ecto-CK2 activity was increased on cancer cells relative to normal fibroblasts and blood cells. Therefore, ecto-CK2 appears to be an additional factor protecting cells from complement-mediated lysis, probably by phosphorylation/inhibition of complement C9.

Casein Kinase II↗
PubMed2004

Cell signals transduced by complement.

The complement system is composed of soluble blood plasma proteins and cell membrane proteins. A major function of the soluble complement proteins is to bind to and destroy invading pathogens. The membrane proteins of the complement system are divided into complement receptors and complement regulatory proteins. Complement receptors on phagocytic cells promote binding and engulfment of pathogens coated with complement opsonins, whereas complement regulatory proteins protect healthy tissues from accidental damage by the soluble complement proteins. Upon binding of complement proteins or protein fragments that are generated during complement activation, these receptors and regulatory proteins transduce various signals into cells bearing them. The complement membrane attack complex C5b-9 binds to cell membranes, independent of any receptor, and also activates multiple signaling pathways. The receptor-dependent and -independent signals transduced by complement components are of great consequence to health and disease. Complement plays an important role in immunoregulation by activating B and T lymphocytes. It may also exert pro- or anti-apoptotic effects on various cell types. At sublytic doses, the complement membrane attack complex has wide-range effects on many cell types leading to cellular responses, such as secretion, adherence, aggregation, chemotaxis and even cell division. Sublytic complement also induces increased cell resistance to lytic doses of complement. Finally, certain pathogens take advantage of complement membrane proteins to gain entry into cells. The emerging data on these complement-related signaling pathways is hereby described.

Animals↗
PubMed2004

Fas ligand as a tool for immunosuppression and generation of immune tolerance.

The role of Fas ligand (FasL) in physiologically limiting immune responses and maintaining immune-privileged sites has led to a body of research aiming to confer protection to allogeneic grafts by expressing FasL on the allogeneic tissue or by administrating FasL-transduced donor dendritic cells. In addition, several studies have used FasL to abrogate autoimmune responses. This review presents the results of these studies and discusses the problems associated with FasL usage.

Animals↗