Characterization of L-CCR, an Orphan Chemokine Receptor Expressed By Dendritic Cells
Posted on: Thursday, 17 June 2004, 06:00 CDT
L-CCR is an orphan seven transmembrane G-prolein-coupled receptor that shows about 50% homology with CCR1, an inflammatory chemokine receptor. The highest degree of sequence similarity is with HCR that may represent its human orthologue. Functional studies (chemotaxis, calcium fluxes, and internalisation assays) undertaken in our laboratory using cell transfectants for L-CCR have failed to identify the natural ligand of L-CCR amongst known chemokines and chemoattractant molecules. Expression of L-CCR mRNA is found in neutrophils and activated macrophages. L-CCR is also expressed at low levels by immature dendritic cells and its expression is rapidly (2 hrs) induced following stimulation with LPS and CD40L but not TNF- a. L-CCR expression in dendritic cells is transient and precedes but does not overlap with CCR7 expression. Therefore, L-CCR may play a role in the early phases of dendritic cell maturation. Anti L-CCR specific monoclonal antibodies were generated and used to study L- CCR distribution and regulation in vitro and in vivo. To assess the in vivo role of L-CCR we have generated L-CCR gene defective mice. L- CCRV- mice are healthy, bred according to Mendelian inheritance patterns, and displays normal survival, growth and fertility with no gross abnormalities found in major organs. Functional studies on L- CCR-/- mice are currently ongoing.
K. Otcro1, E. Dander1, S. Bernasconi1, E. Hirsch2, C. Garlanda1, A. Mantovani1,3, A. Vecchi1, S. Sozzani1,4
1Mario Negri Institute, Milan, Italy; Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy; Institute of General Pathology, University of Milan, Milan, Italy; ''Department of General Pathology and Immunology, University of Brescia, Brescia, Italy
Copyright Edizioni Minerva Medica Mar 2004
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