Molecular Cloning of a Novel Human CC Chemokine Liver and Activation-regulated Chemokine (LARC) Expressed in Liver

Abstract

Partial overlapping cDNA sequences likely to encode a novel human CC chemokine were identified from the GenBank Expressed Sequence Tag data base. Using these sequences, we isolated full-length cDNA encoding a protein of 96 amino acid residues with 20 -28% identity to other CC chemokines. By Northern blot, this chemokine was mainly expressed in liver among various tissues and strongly induced in several human cell lines by phorbol myristate acetate. We thus designated this chemokine as LARC from Liver and Activation-Regulated Chemokine. We mapped the LARC gene close to the chromosomal marker D2S159 at chromosome 2q33-q37 by somatic cell and radiation hybrid mappings and isolated two yeast artificial chromosome clones containing the LARC gene from this region. To prepare LARC, we subcloned the cDNA into a baculovirus vector and expressed it in insect cells. The secreted protein started at Ala-27 and was significantly chemotactic for lymphocytes. At a concentration of 1 g/ml, it also showed a weak chemotactic activity for granulocytes. Unlike other CC chemokines, however, LARC was not chemotactic for monocytic THP-1 cells or blood monocytes. LARC tagged with secreted alkaline phosphatase-(His) 6 bound specifically to lymphocytes, the binding being competed only by LARC and not by other CC or CXC chemokines. Scatchard analysis revealed a single class of receptors for LARC on lymphocytes with a K d of 0.4 nM and 2100 sites/cell. Collectively, LARC is a novel CC chemokine, which may represent a new group of CC chemokines localized on chromosome 2.

ESE-1, an Enterocyte-specific Ets Transcription Factor, Regulates MIP-3α Gene Expression in Caco-2 Human Colonic Epithelial Cells

“…Further analysis of this sequence using the TransFac data base (35), identified putative binding sites for NF-B, C/EBP, AP-1, c-Ets, and Sp1/CACCC binding protein within the first 250 bp of the promoter. A previous study by Hieshima et al (8), using 5Ј rapid amplifica-tion of cDNA ends, identified a transcription initiation point 58-bp upstream from the MIP-3␣ start codon.…”

Increased Endogenous Estrogen Synthesis Leads to the Sequential Induction of Prostatic Inflammation (Prostatitis) and Prostatic Pre-Malignancy

“…CCL20 is strongly chemotactic for lymphocytes and also weakly attracts neutrophils and elicits its effects on target cells by binding and activating the chemokine receptor CCR6. 52 The profound increase in CCL20 expression (ϳ25ϫ) and its receptor CCR6 (ϳ5ϫ) is of particular significance as increased CCR6 expression has been associated with advanced and aggressive PCa and CCL20/CCR6 have also been suggested as novel treatment target molecules for PCa. 31 The increased expression of CCL8, CCR5, and CCR2 in the AROMϩ tissues is also particularly significant (increased ϳ10ϫ, ϳ3ϫ, and ϳ4ϫ, respectively).…”

Chemokines: signal lamps for trafficking of T and B cells for development and effector function

“…Chemokines are good candidates to regulate the ordered localization and migration of T cell progenitors. Thymus expresses a number of chemokines including MDC/STCP-1 [24,25], TECK [26], TARC [27], SDF-1 [28], LARC/MIP-3␣/Exodus [29][30][31], murine thymusderived chemotactic agent 4 (TCA4) [32], and CK␤-11/MIP-3␤/ ELC [31,33] at high levels ( Table 3). TECK is expressed by thymic dendritic cells but not by bone marrow dendritic cells [26].…”

“…Only DP and CD8 ϩ SP subsets, but not DN and CD4 ϩ SP subsets, expressed CCR5, a major receptor for MIP-1␤, suggesting that other chemokine receptors such as CCR8, a recently identified MIP-1␤ receptor, may also be involved in the thymocyte chemotaxis to MIP-1␤ [36]. Other thymus-expressed chemokines, TARC, LARC, MDC/STCP-1, and murine TCA4, attract mature leukocytes: TARC attracts T cell lines [27]; LARC attracts resting lymphocytes [30]; MDC/STCP-1 attracts activated T cells, monocytederived dendritic cells, monocytes, and NK cells [24,25]; TCA4 attracts mature T cells and cultured mesangial cells [32]. Recirculation of mature T cells to thymus was suggested to be a negative regulation mechanism of T lymphopoiesis [37,38].…”