Proteoglycans regulate the chemotaxis of dendritic cells derived from human peripheral blood monocytes.
Dendritic cells (DCs) are a type of antigen-presenting cell which play an essential role in the immune system. The transition from immature DC (iDCs) to mature DCs (mDCs) requires appropriate maturation stimuli, such as pro-inflammatory cytokines or pathogen-derived components. Proteoglycans (PGs), which are composed of core proteins and the glycosaminoglycans that bind to them, are one of the main components of the extracellular matrix around pathogens such as bacteria. This study investigated the effects of PG extracted from the nasal septum cartilage of whale (W-PG) on the maturation of DCs derived from human peripheral blood monocytes. iDCs were prepared from human monocytes using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The iDCs were stimulated by W-PG alone. In another type of experiment, the iDCs were stimulated by MIX (tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and prostaglandin E(2) (PGE(2))) or a combination of MIX plus W-PG. The stimulation of W-PG alone did not induce the phenotypic maturation from iDCs. However, W-PG promoted the up-regulation of chemokine receptor CCR7-surface expression and the chemotactic responsiveness to CCR7 ligand macrophage inflammatory protein-3beta on MIX-stimulated mDCs although W-PG did not influence matrix metalloproteinase-9 activity which is an important factor in DC migration through the extracellular matrix. The findings that W-PG can selectively regulate the chemotactic activity of DCs in vitro under inflammatory conditions therefore indicate that the interaction of PGs with immune cells including DCs plays an important role in the immune response under the milieu of innate immunity.
Department of Radiological Life Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
Hironori
H
Yoshino
Kenji
K
Takahashi
Satoru
S
Monzen
Ikuo
I
Kashiwakura
D000818:Animals; D002356:Cartilage; D002454:Cell Differentiation / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015847:Interleukin-4; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D009300:Nasal Septum; D011509:Proteoglycans / Q000494:pharmacology*; D054400:Receptors, CCR7 / Q000378:metabolism; D015854:Up-Regulation; D014907:Whales
D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D011509:Proteoglycans; D054400:Receptors, CCR7; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone