Neuronal expression of a functional receptor for the C5a complement activation fragment

The present studies were undertaken to determine whether neuronal subsets i n normal brains constitutively express functionally competent C5a receptors , In situ hybridization studies coupled with immunohistochemical approaches revealed that most neurons in the hippocampal formation, many pyramidal co rtical neurons, and cerebellar Purkinje neurons in normal human and murine brains constitutively express C5a receptors, Neuronal C5a receptors bound C 5a-coated fluorescent microspheres, and primary rodent hippocampal neurons responded to C5a with increased calcium fluxes via a pertussis-sensitive, p resumably Gi-coupled protein. Additional studies with human neuroblastoma c ells conducted to address the functional role of C5a receptors revealed tha t C5a triggered rapid activation of protein kinase C and activation and nuc lear translocation of the NF-kappaB transcription factor. In addition, C5a was found to be mitogenic for undifferentiated human neuroblastoma cells, a novel action for the C5aR, In contrast, C5a protected terminally different iated human neuroblastoma cells from toxicity mediated by the amyloid A bet a peptide. Thus, normal rodent hippocampal neurons as well as undifferentia ted and differentiated human neuroblastoma cells express functional C5a rec eptors, These results have implications for understanding the role of neuro nal C5aR receptors in normal neuronal development, neuronal homeostasis, an d neuroinflammatory conditions such as Alzheimer's disease.