Recombinant Mouse CX3CL1/Fractalkine (aa 29-102) Protein, CF

Fractalkine, designated CX3CL1 and also known as neurotactin, is the only member of the CX3C, or delta, chemokine subfamily (1-4). Unlike most other chemokines, CX3CL1 is a type I transmembrane (TM) adhesion protein (1). The mouse CX3CL1 cDNA encodes 395 amino acids (aa), including a signal sequence (aa 1-24), a chemokine domain (aa 25-100), a mucin stalk region (aa 101-336), a transmembrane segment (aa 337-357), and a cytoplasmic tail (aa 358-395). The chemokine domain contains binding and chemotactic determinants, while the mucin stalk appears to function only as a spacer (4, 5). Mouse CX3CL1 shares 85% and 78% aa sequence identity with rat and human CX3CL1, respectively, within the chemokine domain, but lower sequence identity within other domains. CX3CL1 is up-regulated by pro-inflammatory stimuli, especially IFN‑ gamma and TNF‑ alpha, on cell types including macrophages, dendritic cells, endothelium, neurons, smooth muscle and epithelium lining the intestines and other tubules (1, 8, 9). The 40 kDa, 7‑TM non‑glycosylated G‑protein coupled CX3CL1 receptor, CX3CR1, is expressed by cytotoxic effector cells and cytokine producers, including type I helper and cytotoxic T cells, gamma delta T cells, CD16⁺ NK cells, monocytes and microglia (1, 2). The 95-100 kDa TM CX3CL1 can be inducibly cleaved near the TM segment by ADAM10 or ADAM17 to generate a 60-80 kDa soluble form (6, 7). TM CX3CL1 functions as an adhesion molecule, while both forms are chemoattractants for target cells expressing CX3CR1 (1, 2). During extravasation, membrane‑bound CX3CL1 traps leukocytes, then is cleaved to allow diapedesis (6). In coronary artery disease, soluble CX3CL1 and CD8⁺ T cell CX3CR1 are overexpressed and appear to contribute to pathogenesis (1, 10). In the brain, CX3CL1/CX3CR1 interaction protects against microglial neurotoxicity (11). CX3CL1 also contributes to wound healing by recruiting macrophages, and to bone resorption by recruiting and mediating adhesion of osteoclast precursors (12, 13).