ReviewBioenergetics of immune functions: fundamental and therapeutic aspects
Section snippets
Cellular energy metabolism
The free energy used by cells comes from respiration or glycolysis. In aerobic organisms, oxidation of fuel molecules to drive oxidative phosphorylation is the major energy source1. ATP is the principal immediate donor of free energy. Turnover is very high: an ATP molecule is typically consumed within a minute of its formation. The reactions of ATP production and consumption can be centred around the proton-motive force (Δp) and divided into substrate oxidation (all reactions between the
Effect of energy deficit on immune function
Late stages of septic and haemorrhagic shock are situations of energy deficit, in which cellular energy stores and oxygen supply become inadequate. ATP-dependent cellular functions, including those of immune cells such as lymphocytes and macrophages, become increasingly restricted. Presumably, the marked immunosuppression of patients in these clinical situations is due to reduced ability to synthesize lymphokines, decreased macrophage cytotoxicity and abnormal antigen presentation2. Also,
Housekeeping functions
Synthesis of macromolecules and ion transport are important processes for both housekeeping and specific immune functions. Housekeeping functions include maintenance of ionic integrity, volume regulation and cell growth (Fig. 2).
The pattern of energy metabolism is known in detail for lymphocytes. In quiescent rat thymocytes only 50% of the oxygen consumption has been assigned to specific processes10. The oxygen is mainly used by mitochondria, whereas nonmitochondrial oxygen consumption is
Specific immune functions
Most of the activities of immune cells depend directly or indirectly on cellular energy supply (Fig. 2). This includes significant ATP consumption for the following specific immune functions.
Therapeutic targeting of energy metabolism in immune cells
Processes of energy metabolism are important targets for immunotherapy. Examples of drugs with therapeutically relevant bioenergetic effects but not discussed here are listed in Table 1.
Conclusions
Like all living cells, immunocompetent cells require sufficient energy to maintain cellular integrity and basal metabolism. Most of their specific immune functions directly or indirectly use ATP or other high-energy nucleoside triphosphates. This energy supply is crucial for processes such as motor functions, antigen processing and presentation, and effector functions. Therefore, these processes are important targets for immunotherapy. By highlighting the effects of drugs on the energy
Acknowledgements
This work was supported by grants from the Deutsche Forschungsgemeinschaft (Bu 1015/1-1), Deutscher Akademischer Austauschdienst (D/96/17655) and Boehringer Ingelheim Fonds to F.B.
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