Fractalkine (CX(3)CL1) is the first described chemokine that can exist eith
er as a soluble protein or as a membrane-bound molecule. Both forms of frac
talkine can mediate adhesion of cells expressing its receptor, CX(3)CR1. Th
is activity, together with its expression on endothelial cells, suggests th
at fractalkine might mediate adhesion of leukocytes to the endothelium duri
ng inflammation. Fractalkine is also highly expressed in neurons, and its r
eceptor, CX(3)CR1, is expressed on glial cells, To determine the biologic r
ole of fractalkine, we used targeted gene disruption to generate fractalkin
e-deficient mice. These mice did not exhibit overt behavioral abnormalities
, and histologic analysis of their brains did not reveal any gross changes
compared to wild-type mice. In addition, these mice had normal hematologic
profiles except for a decrease in the number of blood leukocytes expressing
the cell surface marker F4/80. The cellular composition of their lymph nod
es did not differ significantly from that of wild-type mice. Similarly, the
responses of fractalkine(-/-) mice to a variety of inflammatory stimuli we
re indistinguishable from those of wild-type mice.