Fractalkine and fractalkine receptors in human neurons and glial cells

Abstract

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 transcriptasepolymerase 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.

Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation

“…CX 3 CL1 is prominently expressed by multiple non-hematopoietic cell types, including muscle, neurons, renal cells, epithelial and endothelial cells, under inflammatory and pathological conditions. 15,23,[44][45][46][47][48][49][50] Under those conditions, CX 3 CL1 may facilitate the adhesion and transmigration of Mos. 51 Additionally, it has been recently proposed that a direct and evolutionary conserved role for CX 3 CR1-CX 3 CL1 interactions is involved in Mo survival.…”

“…Accordingly, the importance of the CX 3 CR1-CX 3 CL1 axis in pathogenesis has been highlighted in several studies. It is involved in atherosclerosis, 26,[41][42]45,46 vascular and renal inflammation 37,48,53 and cancer, 50 it stimulates actin reorganization in microglia 49,54 and it promotes leukocyte-renal endothelial cell interactions during hemolytic uremic syndrome, thereby contributing to the renal microvascular dysfunction and thrombotic microangiopathy. 55,56 To improve our understanding of the biological role of the interaction between fractalkine and CX 3 CR1 in monocytic populations, we analyzed CX 3 CR1 surface protein expression as well as mRNA expression in freshly Mo, MAC and DC populations.…”

Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

“…The physiological relevance of membrane and soluble FKN is not known; however, it is currently thought that membrane-associated FKN (m-FKN) predominantly mediates cell adhesion, whereas the soluble protein FKN (s-FKN) acts as a chemoattractant (22,30). The unique receptor for FKN, CX 3 CR1, is expressed on monocytes (3), subsets of T lymphocytes (24,45), mast cells (48), natural killer cells (33), dendritic cells (16), platelets (52), neurons, astrocytes, and microglial cells (31,40,42) and mediates both the adhesive and chemotactic functions of FKN.…”

Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease

“…Some studies identify the generation of annexin I and membrane PS exposure that appears to be necessary to connect an apoptotic cell with a phagocyte [12]. Secreted factors by either apoptotic or phagocytic cells, such as milk fat globule-EGF-factor 8 [84], fractalkine [86], and lipid lysophosphosphatidylcholine [113], have also been shown to assist with the phagocytic removal of injured cells.…”