Human Macrophage–derived Chemokine (MDC), a Novel Chemoattractant for Monocytes, Monocyte-derived Dendritic Cells, and Natural Killer Cells

Abstract

A cDNA encoding a novel human chemokine was isolated by random sequencing of cDNA clones from human monocyte-derived macrophages. This protein has been termed macrophagederived chemokine (MDC) because it appears to be synthesized specifically by cells of the macrophage lineage. MDC has the four-cysteine motif and other highly conserved residues characteristic of CC chemokines, but it shares <35% identity with any of the known chemokines. Recombinant MDC was expressed in Chinese hamster ovary cells and purified by heparin– Sepharose chromatography. NH2-terminal sequencing and mass spectrophotometry were used to verify the NH2 terminus and molecular mass of recombinant MDC (8,081 dalton). In microchamber migration assays, monocyte-derived dendritic cells and IL-2–activated natural killer cells migrated to MDC in a dose-dependent manner, with a maximal chemotactic response at 1 ng/ml. Freshly isolated monocytes also migrated toward MDC, but with a peak response at 100 ng/ml MDC. Northern analyses indicated MDC is highly expressed in macrophages and in monocyte-derived dendritic cells, but not in monocytes, natural killer cells, or several cell lines of epithelial, endothelial, or fibroblast origin. High expression was also detected in normal thymus and less expression in lung and spleen. Unlike most other CC chemokines, MDC is encoded on human chromosome 16. MDC is thus a unique member of the CC chemokine family that may play a fundamental role in the function of dendritic cells, natural killer cells, and monocytes.

Macrophage-derived chemokine gene transfer results in tumor regression in murine lung carcinoma model through efficient induction of antitumor immunity

“…36 MDC is a potent chemoattractant for DC, NK cells, Th2 and Tc2 subsets of T cells. 1,2,6 The functional receptor for MDC is the CC chemokine receptor 4 (CCR4), which is preferentially expressed on blood T cells, particularly CD4 + T cells of the Th2 phenotype. 2 MDC is thought to…”

“…MDC was shown to be a potent chemoattractant for DC in variGene Therapy ous animal models. 1,2 We therefore intended to verify whether adenovirus-mediated MDC gene transfer could attract and activate DC in tumor-bearing mice. We visualized mouse DC using a fluorescent marker (PKH-26) 3 days after AdMDC administration.…”

“…High expression is detected in normal thymus. MDC is a potent chemoattractant for dendritic cells (DC), natural killer (NK) cells and Th2 subset of T cells 1,2 and is involved in chronic inflammation or homing of DC and lymphocytes. 3,4 Recent studies have demonstrated a pivotal role of MDC in the protection of mice from cecal ligation and puncture-induced lethality.…”

Macrophage-Derived Chemokine Expression in Classical Hodgkin's Lymphoma: Application of Tissue Microarrays

“…Macrophage-derived chemokine (MDC) and TARC are CC chemokines that function through the CCR4 receptor, promoting chemotaxis of monocytes, monocyte-derived dendritic cells, eosinophils, and NK cells (6). MDC is constitutively expressed by thymic medullary epithelial cells and macrophages and by activated B and T lymphocytes (7,8).…”

Cancer cell-derived IL-1α induces CCL22 and the recruitment of regulatory T cells

“…2 CCL22 is constitutively expressed in macrophages, monocytes and dendritic cells and is inducible in many other immune cells such as Th2 cells and B lymphocytes as well as in epithelial cells. [3][4][5][6] CCL22 is the functional ligand for CCR4, a chemokine receptor expressed on the surface of Th2 cells and regulatory T cells (Treg). 7,8 Elevated levels of CCL22 have been described in many human tumors, including B-CLL, Hodgkin lymphoma, breast, lung and gastrointestinal cancers.…”