Innate Immunity and Resistance to Tolerogenesis in Allotransplantation

The development of immunosuppressive drugs to control adaptive immune responses has led to the success of transplantation as a therapy for end-stage organ failure. However, these agents are largely ineffective in suppressing components of the innate immune system. This distinction has gained in clinical significance as mounting evidence now indicates that innate immune responses play important roles in the acute and chronic rejection of whole organ allografts. For instance, whereas clinical interest in natural killer (NK) cells was once largely confined to the field of bone marrow transplantation, recent findings suggest that these cells can also participate in the acute rejection of cardiac allografts and prevent tolerance induction. Stimulation of Toll-like receptors (TLRs), another important component of innate immunity, by endogenous ligands released in response to ischemia/reperfusion is now known to cause an inflammatory milieu favorable to graft rejection and abrogation of tolerance. Emerging data suggest that activation of complement is linked to acute rejection and interferes with tolerance. In summary, the conventional wisdom that the innate immune system is of little importance in whole organ transplantation is no longer tenable. The addition of strategies that target TLRs, NK cells, complement, and other components of the innate immune system will be necessary to eventually achieve long-term tolerance to human allograft recipients

A negative correlation between the induction of long-term potentiation and activation of immediate early genes

In the present study we examined the relationship between the induction of long-term potentiation (LTP) in the dentate gyrus of anesthetized rats and activation of immediate early genes (IEGs; c-fos and zif/268) using several different high-frequency stimulation paradigms. Stimulation parameters that effectively induced LTP were not associated with IEG activation. Conversely, stimulation parameters that failed to induce LTP consistently resulted in IEG activation. These results suggest that there is a negative correlation between IEG activation and LTP, and that activation of IEGs is neither necessary nor sufficient for the induction of LTP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56200/1/schreiberMBRES91.pd

Neurohormones et melanomes : mise en evidence des immunoreactivites TRH et Met-Enk dans des tumeurs et des lignees cellulaires de melanomes malins humains, effet de la TRH sur ces lignees

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Long-term potentiation is associated with increased [3H]AMPA binding in rat hippocampus

The location and nature of the changes underlying long-term potentiation (LTP) remain controversial issues. In this study, we tested the possibility that changes in binding properties of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA/quisqualate and N-methyl-D-aspartate (NMDA) subtype of glutamate receptors are associated with LTP. LTP was elicited in vivo by stimulation of the perforant pathway in anesthetized rats. One hour following stimulation the animals were sacrificed. We performed quantitative ligand binding autoradiography on frozen brain sections using [3H]AMPA and [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([3H]TCP) to label the AMPA/quisqualate and the NMDA receptors, respectively. No changes in [3H]TCP binding were detected in any of the treatment groups. However, increases in [3H]AMPA binding were observed only in animals that exhibited LTP. These increases were bilateral and present in several subfields of the hippocampus and cortical areas. Administration of the NMDA receptor antagonist, ketamine, prior to tetanic stimulation prevented both the increase in binding and the induction of LTP. These results suggest that changes in the characteristics of AMPA/quisqualate receptors are a biochemical correlate of LTP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56201/1/toccoBRES92.pd

Emergence neophobia correlates with hippocampal and cortical glutamate receptor binding in rats

Previous work from our laboratory indicated that emergence neophobia is highly correlated with perforant path long-term potentiation (LTP) in rats. In the present study, we examined the relationship between hippocampal and cortical alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors and emergence behavior in rats. Emergence neophobia was assessed in an exploratory task that provided a choice between a novel alley and a familiar nest box. Quantitative autoradiography using radiolabeled ligands specific for the AMPA subclass of glutamate receptors was performed on frozen brain sections. Both [3H]AMPA and [3H]CNQX (6-cyano-7-nitro-[3H]quinoxaline- 2,3-dione, an AMPA receptor antagonist) binding in the dentate gyrus (stratum moleculare), hippocampal area CA1 (stratum radiatum), and the parietal cortex overlying the hippocampus were significantly correlated with emergence behavior. The correlations indicated that neophobic rats, which had longer latencies to enter the novel alley, made fewer entries into the alley, and spent less time in the novel alley during a 10-min test than their neophilic counterparts, had higher levels of AMPA receptor binding. These results suggest that individual differences in specific hippocampal AMPA receptors reflect variability in a specific class of hippocampal-dependent behaviors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56208/1/marenBNB94.pd