title: 3,4-dichloropropionaniline suppresses normal macrophage function.
abstract: Macrophages are a critical part of the innate immune response and natural surveillance mechanisms. As such, proper macrophage function is crucial for engulfing bacterial pathogens through phagocytosis and destroying them by generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The production of a number of cytokines by macrophages, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, plays an important role in the initiation of the acquired immune response creating an inflammatory environment favorable for fighting a bacterial infection. 3,4-Dichloropropionaniline (DCPA) suppresses several inflammatory parameters, including TNF-alpha production through a mechanism where nuclear factor-kappaB (NF-kappaB)-DNA binding is inhibited but not entirely abrogated. The goal of the present study was to evaluate the effects of DCPA on the inflammatory mediators of macrophages, including ROS and RNS in both murine peritoneal exudate cells and the human monocytic cell line, THP-1. The ability to perform phagocytosis and directly kill Listeria monocytogenes was also assessed. The results indicate that DCPA decreases the ability of both types of macrophages to phagocytize beads and generate both types of reactive species, which was correlated with a decrement in listericidal activity. These results demonstrate that DCPA has profound effects on macrophage function and provide insight into the potential mechanisms of immunosuppression by DCPA.
authors.affiliation: Department of Microbiology, Immunology and Cell Biology, Center for Immunopathology and Microbial Pathogenesis, West Virginia University, Morgantown, WV 26506-9177, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Ustyugova
authors.forename: Laura L
authors.initials: LL
authors.lastname: Frost
authors.forename: Knox
authors.initials: K
authors.lastname: Van Dyke
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Brundage
authors.forename: Rosana
authors.initials: R
authors.lastname: Schafer
authors.forename: John B
authors.initials: JB
authors.lastname: Barnett
mesh_terms: D000818:Animals; D001770:Blood Bactericidal Activity / Q000187:drug effects; D015153:Blotting, Western; D001822:Body Burden; D002469:Cell Separation; D003864:Depression, Chemical; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D008089:Listeria monocytogenes / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010587:Phagocytosis / Q000187:drug effects; D011411:Propanil / Q000633:toxicity*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006540:Herbicides; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D011411:Propanil; D052247:Nitric Oxide Synthase Type II