Metabolic and cellular characterization of immortalized human microglial cells under heat stress

Microglia are able to shift from a resting to an activated state during which they acquire functions typical of primitive forms of mononuclear phagocytes, as well as highly differentiated forms of these cell types. Activation of the microglia after a trauma involves functional readjustments including both the resurrection of basic cell functions and the development of functions implicated in cell-cell interactions. Here, the behaviour of the human microglial cell line CHME-5 was observed after hyperthermia. The strong expression of the inducible form of the hsp70 proteins and their nuclear location, like the more nucleolar presence of the hsc70 proteins seemed to confer heat resistance to the cells. Following minor morphological changes, the observation of the cytoskeleton network during stress recovery revealed a differential sensitivity of actin and tubuline to heat shock. The energy metabolism of both the microglial cell line and the monocyte cell line U937 were compared, under basal conditions, using phosphorus-31 NMR, to discern those phosphorylated metabolites which could be specific of either the monocytic or the macrophagic phenotype. A very high content of phosphocreatine was observed in the microglial clone whereas this compound was absent in monocytes. The lower CHME-5 phosphomonoester content as compared to monocytes also suggested that the microglial cell line displayed a more macrophagic metabolic pattern. After heat shock, the CHME-5 phosphorylated compounds showed large, transient, perturbations. Cells recovered their basal metabolic content 24 h after heat stress. This behaviour, in addition to the expression of inducible hsp70 proteins and the cytoskeleton rearrangement, are indicative of the particular adaptation of the microglial cell line to stress situations.