Fractalkine has been identified as a novel
chemokine that exhibits cell adhesion and chemoattractive properties in the central nervous system (CNS), and the
fractalkine receptors, CX3CR1, are also expressed in the CNS. In the present study, the expression of
fractalkine and
fractalkine receptors was investigated in enriched populations of human CNS neurons, astrocytes, and microglia. In addition, the regulatory role played by
protein kinase C (PKC) in
fractalkine secretion in neurons was determined in A1 human hybrid neuronal cell line produced between a human cerebral neuron and a human
neuroblastoma cell. Human neurons and astrocytes expressed
fractalkine mRNA as determined by the revserse
transcriptase-polymerase chain reaction (RT-PCR) analysis, while human microglia preparation did not express the
fractalkine message. Human neurons and microglia expressed CX3CR1
mRNA, but astrocytes did not. These results suggest that
fractalkine secreted by CNS neurons and astrocytes produce
biological effects in neurons and microglia. Although
phorbol ester did not change the expression of
fractalkine mRNA level in A1 hybrid neurons, it did upregulate
fractalkine secretion over unstimulated controls. This upregulation of
fractalkine production was suppressed by the treatment with Ro32-0432, a PKC inhibitor. These results indicate that intracellular signals transduced by PKC play an important role in the regulation of soluble
fractalkine at the post-transcriptional level in human neurons. As for the
biological function of
fractalkine, extracellularly applied
fractalkine increased the number of
bromodeoxyuridine-labeled microglia 3-fold over the untreated controls, indicating
fractalkine induces proliferation of human microglia. These observations suggest that
fractalkine released by injured neurons could induce proliferation, activation and/or migration of microglia at the injured brain sites.