Met-RANTES

Grone HJ, Weber C, Weber KS, et al. Met-RANTES reduces vascular and tubular damage during acute renal transplant rejection blocking monocyte arrest and recruitment. FASEB J 1999 13 1371-1383. 

Eisner J, Petering H, Hochstetter R, et al. The CC chemokine antagonist Met-RANTES inhibits eosinophil effector functions through the chemokine receptors CCR1 and CCR3. Eur J Immunol 1997 27(ll) 2892-2898. 

E4. Eisner, J., Petering, H., Kimmig, D., Wells, T. N., Proudfoot, A. E., and Kapp, A., The CC chemokine receptor antagonist met-RANTES inhibits eosinophil effector functions. Int. Arch. Allergy Immunol. 118, 462—465 (1999). 

Fig. 4. Visualization of several purified RANTES proteins on a Coomassie stained SDS page Lanes 1 and 2, 6xHis-tagged RANTES expressed in the periplasmic space of E. coli Lane 3, Met-RANTES expressed in the cytoplasm of E. coli and purified from inclusion bodies Lane 4, eucaryotic expressed 6xHis-tagged RANTES.

Fig. 1. Gel-filtration of the solubilized inclusion bodies from E. coli cells expressing Met-RANTES. 100 mL were loaded onto a Sephacryl 200 HR column (5 cm diam x 100 cm) and the elution carried out at a flow rate of 2 mL/min as described in Subheading 3.2. The fractions were pooled as indicated.

Fig. 1. Downmodulation of CCR5 from the surface of stably transfected CHO-CCR5 cells with RANTES, AOP-RANTES, and Met-RANTES. Staining of CCR5 was performed with the CCR5-antibody MC-1. (Adapted with permission from ref. 3.)...

RANTES, which can signal through CCRl, CCR3, or CCR5, has been modified to Met-RANTES, as described earlier. Met-RANTES acts as a functional antagonist and blocks human eosinophil chemotaxis, Ca + flux, actin polymerization,and release of ROS after stimulation with RANTES, MCP-3, and eotaxin (148). Met-RANTES apparently antagonizes... 

Grone, H.J., Weber, C., Weber, KC., Grone, E.F., Rabelink, T, Kher, C.M., Wells, T.C., Proudfoot, A.E., Schlondorff D., and Nelson, P.J. (1999) Met-RANTES reduces vascular and tubular damage during acute renal transplant rejection blocking monocyte arrest and recruitment The FASEB Journal, 13, 1371-1383. 

CCR5 CCL4 CCL5 CCR1 mice had attenuated form of EAE CCRl antagonist BX 471 reduced EAE in rat AntiCCL3 antibody prevented onset EAE AANA -RANTES had inhibitory effect on EAE Antagonist Met-RANTES had no effect on EAE... 

Matsui, M. et al. (2002) Treatment of experimental autoimmune encephalomyelitis with the chemokine receptor antagonist Met-RANTES. Journal of Neuroimmunology, 128, 16-22. 

Extension of the N-terminus of RANTES by the chemical coupling of a five-carbon alkyl chain to the oxidized N-terminal Ser residue produces a modified RANTES protein called aminooxy pentane RANTES (AOP-RANTES). This protein was found to have an increased affinity over RANTES and Met-RANTES for CCR5 (34) and in addition has a greater affinity for CCRl and CCR3 (A. Proudfoot, unpublished results). Whereas neither protein-induced chemotaxis of freshly isolated PBMCs, both were capable of calcium mobilization in CHO cells that had been transfected to express high levels of CCR5 receptors (35). Thus modifications of the N terminus of RANTES result in partial agonists, and their ability to induce cellular responses is probably dependent on the number of receptors expressed at the cell surface. 

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