CHEMOKINE VARIANTS AND METHODS OF USE

摘要

The present invention provides the nucleotide and amino acid sequence of truncated RANTES (3-68), which has the same amino acid sequence as the wild-type RANTES, but with a Serine/Proline truncation at positions 1 and 2 from the N-terminus, respectively. CD26 is a leukocyte activation marker that possesses dipeptidyl peptidase IV (DPPIV) activity but whose natural substrates and immunological functions had not been previously defined. Several chemokines, including RANTES (regulated on activation, normal T expressed and secreted) are provided, which are substrates for human CD26. The truncated RANTES (3-68) lacked the ability of native RANTES (1-68) to increase the cytosolic calcium concentration in human monocytes, but it still induces this response in macrophages activated with macrophage colony-stimulating factor (M-CSF). RANTES (3-68) retains the ability of stimulate CCR5 receptors and to inhibit the cytopathic effects of HIV-1. The invention provides methods for identifying compounds that affect DPPIV-mediated chemokine cleavage, methods for inhibiting HIV infection and treating individuals having or at risk of having HIV infection, methods for diagnosis and/or prognosis of individuals having a chemokine-associated disorder and methods for accelerating wound healing and angiogenesis, all based on the discovery of DPPIV-mediated cleavage of chemokines.