title: Non-Myeloid Cells are Major Contributors to Innate Immune Responses via Production of Monocyte Chemoattractant Protein-1/CCL2.
abstract: Monocyte chemoattractant protein-1 (MCP-1)/CCL2 is a chemokine regulating the recruitment of monocytes into sites of inflammation and cancer. MCP-1 can be produced by a variety of cell types, such as macrophages, neutrophils, fibroblasts, endothelial cells, and epithelial cells. Notably, macrophages produce high levels of MCP-1 in response to proinflammatory stimuli in vitro, leading to the hypothesis that macrophages are the major source of MCP-1 during inflammatory responses in vivo. In stark contrast to the hypothesis, however, there was no significant reduction in MCP-1 protein or the number of infiltrating macrophages in the peritoneal inflammatory exudates of myeloid cell-specific MCP-1-deficient mice in response to i.p injection of thioglycollate or zymosan A. Furthermore, injection of LPS into skin air pouch also had no effect on local MCP-1 production in myeloid-specific MCP-1-deficient mice. Finally, myeloid-specific MCP-1-deficiency did not reduce MCP-1 mRNA expression or macrophage infiltration in LPS-induced lung injury. These results indicate that non-myeloid cells, in response to a variety of stimulants, play a previously unappreciated role in innate immune responses as the primary source of MCP-1.
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick, MD , USA.
authors.forename: Teizo
authors.initials: T
authors.lastname: Yoshimura
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick, MD , USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Galligan
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick, MD , USA.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick, MD , USA.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick, MD , USA.
authors.forename: Mingyong
authors.initials: M
authors.lastname: Liu
authors.affiliation: Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute , Frederick, MD , USA.
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick, MD , USA.
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
keywords: chemokines; gene knockout mice; inflammation; innate immunity; myeloid cells