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J Biol Chem, Vol. 274, Issue 39, 27505-27512, September 24, 1999
From British Biotech Pharmaceuticals Ltd., Watlington Road,
Oxford OX4 5LY, United Kingdom
The biology of RANTES (regulated on activation
normal T cell expressed) aggregation has been investigated using RANTES
and disaggregated variants, enabling comparison of aggregated,
tetrameric, and dimeric RANTES forms. Disaggregated variants retain
their Gi-type G protein-coupled receptor-mediated
biological activities. A correlation between RANTES aggregation and
cellular activation has been demonstrated. Aggregated RANTES, but not
disaggregated RANTES, activates human T cells, monocytes, and
neutrophils. Dimeric RANTES has lost its cellular activating activity,
rendering it noninflammatory. Macrophage inflammatory protein 1 There is a clear difference in the signaling properties of aggregated
and disaggregated RANTES forms, separating the dual signaling pathways
of RANTES and the enhancing and suppressive effects of RANTES on human
immunodeficiency virus infection. Disaggregated RANTES will be a
valuable tool to explore the biology of RANTES action in human
immunodeficiency virus infection and in inflammatory disease.
,
macrophage inflammatory protein-1
, and erythrocytes are potent
natural antagonists of aggregated RANTES-induced cellular activation.
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