Exogenously-induced, natural killer cell-mediated neuronal killing: a novel pathogenetic mechanism
نویسندگان
چکیده
Many human neurodegenerative diseases are characterized by the idiopathic death of cells narrowly restricted to a subset of neurons in a specific functional neuroanatomic system. Few in vivo models exist for the analysis of these types of degeneration. This report documents the death of sympathetic neurons resident in the superior cervical ganglia of rats after exposure to an exogenous chemical agent, the drug guanethidine, as being mediated by natural killer (NK) cells. This is the first in vivo model of a disorder of the nervous system in which NK cells appear to be the principal effector cell, and thus could serve a central role in dissecting the normal and pathological function of NK cells. In addition, this pathogenetic mechanism appears to represent a novel type of autoimmune reaction that could have a direct bearing on a number of human illnesses.
منابع مشابه
The Smac Mimetic BV6 Improves NK Cell-Mediated Killing of Rhabdomyosarcoma Cells by Simultaneously Targeting Tumor and Effector Cells
Rhabdomyosarcoma (RMS), the most common cancer of connective tissues in pediatrics, is often resistant to conventional therapies. One underlying mechanism of this resistance is the overexpression of Inhibitor of Apoptosis (IAP) proteins, leading to a dysfunctional cell death program within tumor cells. Smac mimetics (SM) are small molecules that can reactivate the cell death program by antagoni...
متن کاملNatural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction.
In the present study, we assessed the susceptibility of freshly isolated neuroblastoma cells to killing mediated by normal human natural killer (NK) cells and analyzed the receptor-ligand interactions that regulate this event. We show that killing of freshly isolated neuroblasts, similar to neuroblastoma cell lines, involves NKp46 and NKp30 (natural cytotoxicity receptors). However, freshly iso...
متن کاملThe Influence of Perforin Expression on the Sensitivity of LAK/NK Killing Against Various Tumor Target Cells
Background: Perforin is known to be important in cytolytic activity mediated by natural killer (NK) cells. Objective: To study the relationship between the efficiency of NK and lymphokine-activated killer (LAK) cells activity, and the expression of perforin and HLA class I molecules. Methods: LAK cells were generated by in vitro culturing of human peripheral blood lymphocytes (PBLs) in the ...
متن کاملMetalloprotease-mediated tumor cell shedding of B7-H6, the ligand of the natural killer cell-activating receptor NKp30.
Natural killer (NK) cells are potent immune effector cells capable of mediating antitumor responses. Thus, during immunoediting, tumor cell populations evolve strategies to escape NK-cell-mediated recognition. In this study, we report a novel mechanism of immune escape involving tumor cell shedding of B7-H6, a ligand for the activating receptor NKp30 that mediates NK-cell binding and NK-cell-me...
متن کاملMicroenvironment and Immunology Metalloprotease-Mediated Tumor Cell Shedding of B7-H6, the Ligand of the Natural Killer Cell–Activating Receptor NKp30
Natural killer (NK) cells are potent immune effector cells capable of mediating antitumor responses. Thus, during immunoediting, tumor cell populations evolve strategies to escape NK-cell–mediated recognition. In this study, we report a novel mechanism of immune escape involving tumor cell shedding of B7-H6, a ligand for the activating receptor NKp30 that mediates NK-cell binding and NK-cell–me...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of Experimental Medicine
دوره 176 شماره
صفحات -
تاریخ انتشار 1992